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miR-1273h-5p suppresses CXCL12 expression and inhibits gastric cancer cell invasion and metastasis

  • Yi-Chen Wang , Song Lu , Xiao-Jiang Zhou , Li Yang , Ping Liu , Lan Zhang , Yuan Hu EMAIL logo and Xian-Zhe Dong EMAIL logo
Published/Copyright: May 16, 2022
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Open Medicine
From the journal Open Medicine Volume 17 Issue 1

Abstract

The aim of this study was to verify the biological function of miR-1273h-5p in gastric cancer (GC) and its underlying mechanisms. The differential expression of microRNAs between GC and tumor-adjacent normal tissues was detected using microarrays, miR-1273h-5p, and chemokine (C-X-C motif) ligand 12 (CXCL12) mRNA, and protein levels were evaluated using polymerase chain reaction and Western blotting methods, cell proliferation, apoptosis, migration, and invasion were determined by CCK-8, flow cytometry, and transwell assay. Compared to tumor-adjacent normal tissue and gastric epithelial mucosa cell line cells, miR-1273h-5p was significantly downregulated in tissues and cells of GC. The overexpression of miR-1273h-5p could inhibit cell proliferation, migration, invasion, and promote cell apoptosis; in contrast, inhibition of miR-1273h-5p expression could reverse this process. Moreover, a significant upregulation of CXCL12 was observed when the miR-1273h-5p was downregulated in GC cells. Additionally, miR-1273h-5p significantly reduces tumor volume and weight. Thus, this study suggests that miR-1273h-5p regulates cell proliferation, migration, invasion, and apoptosis during GC progression by directly binding to CXCL12 mRNA 3′-untranslational regions, which may be a novel diagnostic and therapeutic target in GC.

Keywords: gastric cancer; miR-1273h-5p; proliferation; apoptosis; migration; invasion

1 Introduction

The global incidence and mortality rates of gastric cancer (GC) are relatively high [1,2,3], over 70% of cases occur in developing countries [4]. In addition, most GC patients are diagnosed at the advanced stage with extensive involvement of regional lymph nodes or the metastasis to distant organs [5,6] due to non-specific symptoms during the early stage [7]. Moreover, the invasion and metastasis of tumors are the most common reasons for the death from GC [8], and more than 90% of mortality in GC patients is caused by distal metastasis [9]. miRNAs are endogenous non-coding RNAs with a length of about 19–24 nucleotides; numerous studies have confirmed the correlation between the altered expressions of miRNAs and cancer since the dysregulation of miRNAs participates in several important processes during carcinogenesis [10], such as cell growth, differentiation, and apoptosis [11].

Nowadays, many investigations about microRNAs (miRNAs) have been carried out to assess the etiology of GC [12,13,14]. The APEX1/miR-27a-5p axis functions could alter the regulation of the AKT and MAPK pathways serving as a strong potential set of targets for GC-specific chemotherapies [15]. miR-33b-5p also acted as a potential target by downregulating high mobility group AT-hook 2(HMGA2), an indispensable factor that correlated with proliferation and sensitivity to chemotherapy drug of GC cells [16]. miRNA-765 may modify MDR by controlling the expression of BATF2 which provided the possibility of an effective therapeutic target against GC [17] the upregulated miR-106b in cancer-associated fibroblasts of GC patients can accelerate the invasion by regulating phosphatase and tensin homolog deleted on chromosome 10 [18]. Similarly, the roles of miR-106a [19], miR-181b [20], and miR-21 [21] in the development of GC have been identified. Therefore, miRNAs may be a novel therapeutic target for cancers. Nevertheless, the molecular mechanisms underlying the pathogenesis and development of GC remain largely unexplored.

In our current work, we showed that the expression of miR-1273h-5p was dramatically decreased in GC tissues and GC cells; nonetheless, it remained unclear about its function during the progression of GC. So, the present study was to evaluate the antioncogenic function of miR-1273h-5p in GC, which might provide a novel sight for GC therapy.

2 Materials and methods

2.1 Microarray analysis

A total of 53 pairs of GC and tumor-adjacent normal tissue samples were collected from patients (Table 1) between July 2015 and December 2016, and three pairs of these samples were used for microarray analysis. The tumor-adjacent normal tissues were dissected at 3 cm from the edge of the tumors. Microarray assay and bioinformatics analysis (Gen ontology [GO] and Kyoto Encyclopedia of Genes and Genomes [KEGG] pathway) were performed as described in our previous study [22]. Briefly, approximately 1 µg of total RNA was conjugated with polyA tail using FlashTag™ Biotin HSR Labeling Kit (Affymetrix, Santa Clara, CA, USA). Hybridization was carried out with the labeled RNA at 48°C for 16 h with shaking at 60 rpm for Affymetrix miRNA 4.0 Array. A robust Multichip Analysis algorithm was used to analyze the data. The mRNA–miRNA interaction was predicted using the micode database (http://www.mircode.org/). According to the measured values of mRNA and TarBase database (http://www.microrna.gr/tarbase) forecasts, the miRNA-targeting genes were determined. Combined with the actual differential mRNAs detected using microarray, the negative correlation between miRNA–mRNA was obtained. After predicting the target genes, GO and KEGG pathway analyses were performed. The purpose of these analyses was to identify differentially expressed genes (DEGs) between groups. The data were analyzed using Fisher’s exact test. The P-value was calculated using the Benjamini–Hochberg step-up procedure, followed by rectification using the false discovery rate (FDR) method. P ≤ 0.05 was regarded as statistically significant. Meanwhile, enrichment scores were adopted to analyze the enrichment level of GO and pathways.

Table 1

Clinicopathological features of GC patients

Characteristic n = 53 Proportion (%)
Gender
Male 32 60.38
Female 21 39.62
Age (years) Average age, 53
<60 35 66.04
≥60 18 33.96
Differentiation
Well 36 67.92
Poor 17 32.08
Tumor size (cm)
<5 37 69.81
≥5 16 30.19
Lymph node metastasis
Yes 11 20.75
No 42 79.25
HP infection
Yes 28 52.83
No 25 47.17
CA125 level (ng/mL)
<40 12 22.64
≥40 41 77.36

HP infection – H. pylori infection leading to chronic active gastritis remains the main risk factor for GC. CA125 level – CA125 is most common in the serum of patients with epithelial ovarian tumors. Its positive rate in GC was quite high.

2.2 Cell culture conditions

Human GC cell lines that were used in this study (MGC-803, BGC-823, SGC-7901, and MKN-45) and normal gastric epithelial mucosa cell line (GES-1) were provided by Cancer Hospital Chinese Academy of Medical Sciences (Beijing, China). HEK-293 cells were purchased from FuHeng Bio Co., Ltd. (Shanghai, China). GC cells were maintained in RPMI-1640 medium (BioTeke Corporation, Beijing, China), and GES-1 cells were maintained in Dulbecco’s modified Eagle medium (DMEM) in a condition of 37°C containing 5% CO2. The medium used for cell culture contained 10% fetal bovine serum (FBS; Thermo Fisher Scientific, Inc., Waltham, MA, USA).

2.3 RT-qPCR

GC cells and GES-1 cells were seeded into 6-well plates at a density of 2 × 105 cells/well, after 24 h culture; miRNAs were extracted using miRcute miRNA isolation kit (TIANGEN, Beijing, China). The concentration and purity of miRNA were determined using NanoDrop-2000. The miRNAs were reversely transcribed into complementary DNAs (cDNAs) by miRcute Plus miRNA First-Strand cDNA Synthesis Kit (TIANGEN, Beijing, China), and reverse transcription-polymerase chain reaction (RT-qPCR) was conducted by using miRcute Plus miRNA qPCR Detection Kit (SYBR Green) (TIANGEN, Beijing, China) according to the manufacturer’s instructions. Briefly, initial denaturation step: 94°C for 2 min, melting: 94°C for 20 s, and annealing: 60°C for 34 s. U6 and GAPDH were selected as the housekeeping genes. The primers were synthesized by AuGCT (AuGCT, Beijing, China) as follows: miR-1273h-5p-F: 5′-CTGGGAGGTCAAGGCTGCAGT-3′, miR-1273h-5p-R: 5′-ACTGCAGCCTTGACCTCCCAG-3′; U6-F: 5′-AATCTAGCTGCTGCGGTTCC-3′, U6-R: 5′-GGAACCGCAGCAGCTAGATT-3′; CXCL12-F:5′-CAGATGCCCATGCCGATT-3′, CXCL12-R: 5′TCTGAAGGGCACAGTTTGGA-3′; GAPDH-F: 5′-GTGGAGTCCACTGGCGTCTT-3′, GAPDH-R: 5′-GTGCAGGAGGCATTGCTGAT-3′. The relative expressions of target genes were calculated using the 2−ΔΔCT method.

2.4 Western blot

Western blotting analysis was used to analyze the expression of proteins. Briefly, cell lysis was performed using radio immunoprecipitation assay lysis buffer containing protease and phosphatase inhibitor cocktails, and the protein concentrations were determined using a BCA assay. Subsequently, proteins (50 μg) were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis for separation, after which they were electro-transferred onto a polyvinylidene fluoride membrane. After blocking with 5% BSA for 3 h at room temperature, the membranes were incubated with primary antibodies (CXCL12, Proteintech, 17402-1-AP; β-tubulin, Immunoway, YM3030; GAPDH, Immunoway, YM3029) at 4°C overnight followed by incubation with secondary antibodies (HRP-conjugated Affinipure Goat Anti-Rat IgG (H + L), Proteintech, and SA00001-15) for 2 h. Immunoreactive bands were visualized using a chemiluminescence kit, and the density of the bands was determined using scanning densitometry (Bio-Rad, Hercules, CA, USA).

2.5 Cell transfection and luciferase reporter assay

As described in our previous studies [23], miR-1273h-5p expression plasmids including mimics, inhibitors, and empty plasmid (GV268) were provided by GeneChem Co., Ltd. (Shanghai, China). In this study, “normal con” cells were not transfected, and “negative con” cells were transfected with an empty vector. The wild-type and mutant CXCL12 plasmids were also prepared by GeneChem Co., Ltd. and cloned into luciferase plasmid GV272 (GeneChem). miRNA mimic is a plasmid that can increase the level of miR-1273h-5p, and miRNA inhibitor can inhibit the endogenous level of miR-1273h-5p. MGC-803, BGC-823, and SGC-7901 cells were cultivated in 96-well plates (5 × 103 cells/well) and then transfected with miR-1273h-5p mimics, inhibitors, or negative plasmids at the final concentration of 1.5 μg/mL. The final concentration of transfection reagent Lipofectamine 2000 (Thermo Fisher Scientific, Inc.) was 0.2 μL/well (96-well plates).

In Luciferase Reporter Assay, HEK-293 cells were seeded into a 96-well plate (1 × 104 cells/well). CXCL12 expression luciferase plasmid (GeneChem Co., Ltd. Shanghai, China) and miR-1273h-5p mimics were co-transfected into HEK-293 cells. Then, pRL-TK Renilla luciferase vectors (Promega, Madison, WI, USA) were transfected. Finally, the luciferase activity was determined using Dual-Glo Luciferase Assay System (Promega). All experiments were repeated three times.

In the process of constructing target genes, three sequences capable of forming CXCL12 were found distributed in two transcripts. Hence, two plasmids were constructed which were labeled 1,2 at last (Figure A1).

2.6 Cell proliferation assay

MGC-803, BGC-823, and SGC-7901 cells were seeded into 96-well plates (5 × 103 cells/well) in 200 μL of RPMI-1640 medium. After 24 h of culture, cells were transfected with 1 μL of miR-1273h-5p mimics or inhibitors (0.3 μg/μL) using Lipofectamine 2000 (Thermo Fisher Scientific, Inc.). Cells in the negative control group were transfected with 1 μL of empty plasmid (0.3 μg/μL). After 24 h incubation, 20 μL of CCK-8 reagent was added to each well according to the manufacturer’s protocols; 4 h later, cell viability was evaluated by using 1420 Multilabel Counter (PerkinElmer, USA) according to the absorbance at 450 nm. Each experiment containing five replicated samples was conducted in triplicate.

2.7 Cell apoptosis analysis

GC cells were seeded into 6-well plates (1 × 106 cells/well), followed by 24 h incubation. Subsequently, the cells of “negative con” and “mimics” group cells were transfected with 2 μg/mL of empty plasmid or miR-1273h-5p mimic plasmid, respectively. After 24 h, the cells were collected. After washing with phosphate buffer saline, cells were resuspended with 1X Binding Buffer to achieve a concentration of 5 × 106 cell/mL. Then, cells were stained with Annexin-V FITC and Propidium Iodide Apoptosis Detection Kit (Invitrogen) [24] according to the manufacturer’s protocols. Apoptosis data were analyzed using flow cytometry (FCM; BD Biosciences, Calibur, USA) and Cellquest software. The number of apoptotic cells was equal to the sum of early apoptotic cells and late apoptotic cells. All experiments were conducted in triplicate.

2.8 Transwell assays of tumor cell migration and invasion

The transwell assay (Corning, USA) was performed to evaluate cell migratory and invasive capacity of GC cells. For cell invasion assay, 3.35 mg/mL matrigel matrix (CORNING, 354234) was pre-coated on the top of the upper chamber. Cells were suspended at 5.0 × 105 cells/mL in serum-free DMEM, reserving for the next step. Briefly, the upper and bottom transwell chambers (24-well plates) were coated with 100 μL of serum-free medium and 600 μL containing 20% FBS, respectively. The cells were incubated for 24 h. The cells that did not migrate to the lower surface of the membranes were removed from the upper surface of the transwell chamber by a cotton swab. Those migrated cells were stained with 0.1% crystal violet solution. Cell migration assay was the same as invasion assay, except the upper chambers did not need to be coated with Matrigel matrix. Images were then captured under a digital microscope (Olympus IX81, Japan), and the number of cells was counted by the experimenter in five randomly selected fields for each well; every group conducted three wells; all results were presented as mean ± SD.

2.9 Xenograft tumor model

Male BALB/c-nu mice (n = 30) weighing 14.0–17.0 g, aged 4 weeks, were housed in an environment with a temperature of 22 ± 1°C, relative humidity of 50 ± 1%, and a light/dark cycle of 12/12 h. All animal studies were carried out in compliance with the regulations and guidelines of PLA medical school institutional animal care and conducted according to the AAALAC and the IACUC guidelines.

The mice were randomly divided into three groups after being given adaptive feeding under specific-pathogen-free for 5 days and then subcutaneously injected with 0.2 ml cell suspension (2 × 106 cells/mL in RPMI-1640 containing 10.0% FBS) into the right forearm. The above-mentioned cells fell into three categories: SGC-7901 cells, SGC-7901 cells transfected with miR-1273h-5p mimics, and SGC-7901 cells transfected with miR-1273h-5p-negative plasmid. After 3 weeks, tumor volume and weight were carefully measured. Volume (V) was monitored by measuring the tumor length (L) and width (W) with standard calipers and calculated with the formula of V = (L × W 2) × 0.5.

2.10 Statistical analysis

SPSS22.0 and GraphPad prism 5.0 (GraphPad Software Inc., San Diego, CA, USA) were adopted for all statistical analyses. Each experiment was repeated three times. Experiment data involving two groups were verified using a t-test and expressed as mean ± standard deviation. One-way ANOVA was used for multiple group comparison. Microarray analysis and KEGG pathways of DEGs were analyzed using the standard statistical function of hypergeometric distribution, t-test, and FDR. P < 0.05 was regarded as statistically significant.

  1. Ethics approval: The animal experiment was approved by the Ethics Committee of the Chinese PLA Hospital Medical Laboratory animal Center (China; Approval No. 2019-X15-85). The whole research program including clinical tissue samples has been approved by the Ethics Committee of the Chinese PLA General Hospital.

  2. Informed consent: Written informed consent for publication was obtained from all participants.

3 Results

3.1 Differentially expressed miRNAs in GC tissues and cells

The microarray assay was conducted to identify the differentially expressed miRNAs between gastric tissues and tumor-adjacent normal tissues; 19 miRNAs were overexpressed (ratio, >1.5), and 17 miRNAs were downregulated (ratio, <0.667) in gastric tissues compared with the tumor-adjacent normal tissues (Figure 1a).

Figure 1 The analysis of differentially expressed miRNAs between GC and tumor-adjacent normal tissues. (a) Cluster analysis of differentially expressed miRNAs between GC and tumor-adjacent normal tissues by microarray assay. Each column indicates a sample, and each row shows the expression level of a gene. The green color indicates low expression, and the red color displays high expression. (b) The relative expression of miR-1273h-5p in 53 pairs of GC and tumor-adjacent NC was analyzed using RT-PCR. (c) The relative expression of miR-1273h-5p in GES-1 and GC cells was determined by RT-PCR. *P < 0.05; compared with GES-1 cells, *P < 0.05, **P < 0.01.
Figure 1

The analysis of differentially expressed miRNAs between GC and tumor-adjacent normal tissues. (a) Cluster analysis of differentially expressed miRNAs between GC and tumor-adjacent normal tissues by microarray assay. Each column indicates a sample, and each row shows the expression level of a gene. The green color indicates low expression, and the red color displays high expression. (b) The relative expression of miR-1273h-5p in 53 pairs of GC and tumor-adjacent NC was analyzed using RT-PCR. (c) The relative expression of miR-1273h-5p in GES-1 and GC cells was determined by RT-PCR. *P < 0.05; compared with GES-1 cells, *P < 0.05, **P < 0.01.

Next, the expression of miR-1273h-5p in GC tissues (from 53 GC patients with gastrectomy) was downregulated by 0.31-fold compared with the tumor-adjacent normal tissues (Figure 1b). The expression of miR-1273h-5p in human GC cell lines, such as MGC-803, BGC-823, SGC-7901, and MKN-45 cells, and GES-1 cells was validated using RT-PCR. As shown in Figure 1c, the expression of miR-1273h-5p was decreased in four GC cell lines compared with the GES-1 cell line.

3.2 Impact of miR-1273h-5p on the growth and apoptosis of GC cells

Because the miR-1273h-5p expression was significantly low in GC, we speculated that it might inhibit the growth of GC cells and enhance cell apoptosis. To validate our hypotheses, we transfected miR-1273h-5p mimics in BGC-823, MGC-803, and SGC-7901 cells to upregulate miR-1273h-5p expression and downregulate the miR-1273h-5p expression by transfecting miR-1273h-5p inhibitors into cells. The results of validation confirmed the former hypothesis (Figure A2). Subsequently, a CCK-8 assay was conducted after 48 h of transfection to explore the impact of miR-1273h-5p on the viability of BGC-823, MGC-803, and SGC-7901 cells. When transfected with mimics, the viability of BGC-823, MGC-803, and SGC-7901 cells significantly decreased (Figure 2a, c, and e); in contrast, the viability of cells transfected with miR-1273h-5p inhibitors was increased, especially MGC-803 and SGC-7901 that were significantly increased (Figure 2b, d, and f).

Figure 2 Impact of miR-1273h-5p on GC cell viability. (a and b) Impact of miR-1273h-5p on the proliferation of BGC-823 cells at 24 h after transfection evaluated by CCK-8 assay. Compared to the negative control, the mimic group significantly decreased. (c and d) Effect of miR-1273h-5p on the proliferation of MGC-803 cells at 24 h after transfection evaluated using CCK-8 assay. Compared to negative control group, the proliferation in the mimic group decreased while it increased in the inhibitor group. (e and f) Effect of miR-1273h-5p on the proliferation of SGC-7901 cells at 24 h after transfection evaluated using CCK-8 assay. The mimic group significantly decreased compared to negative control. The inhibitor group had a significant increase in comparison with negative group. All data were expressed as mean ± standard deviation (M ± SD) from three independent experiments compared with the negative control group, *P < 0.05, **P < 0.01.
Figure 2

Impact of miR-1273h-5p on GC cell viability. (a and b) Impact of miR-1273h-5p on the proliferation of BGC-823 cells at 24 h after transfection evaluated by CCK-8 assay. Compared to the negative control, the mimic group significantly decreased. (c and d) Effect of miR-1273h-5p on the proliferation of MGC-803 cells at 24 h after transfection evaluated using CCK-8 assay. Compared to negative control group, the proliferation in the mimic group decreased while it increased in the inhibitor group. (e and f) Effect of miR-1273h-5p on the proliferation of SGC-7901 cells at 24 h after transfection evaluated using CCK-8 assay. The mimic group significantly decreased compared to negative control. The inhibitor group had a significant increase in comparison with negative group. All data were expressed as mean ± standard deviation (M ± SD) from three independent experiments compared with the negative control group, *P < 0.05, **P < 0.01.

PI and Annexin V‑FITC staining were adopted to assess the effect of miR-1273h-5p mimics on cell apoptosis by using FCM (Figure 3a). After the cells were transfected with miR-1273h-5p mimics, the apoptotic rates of BGC-823, MGC-803, and SGC-7901 cells were dramatically enhanced (Figure 3b) compared with the corresponding negative control groups. These findings indicated that miR-1273h-5p had a role in regulating the apoptosis of GC cells.

Figure 3 Effect of miR-1273h-5p on GC cell apoptosis. (a) Effect of miR-1273h-5p on apoptosis of BGC-823, MGC-803, and SGC-7901 cells at 24 h after transfection evaluated using FCM. (b) Apoptotic rates of BGC-823, MGC-803, and SGC-7901 cells at 24 h after transfection of miR-1273h-5p mimic. Compared to the negative control, the apoptosis ratio of miR-1273h-5p mimics was significantly increased. All data were expressed as M ± SD from three independent experiments compared with the negative control group, *P < 0.05, **P < 0.01.
Figure 3

Effect of miR-1273h-5p on GC cell apoptosis. (a) Effect of miR-1273h-5p on apoptosis of BGC-823, MGC-803, and SGC-7901 cells at 24 h after transfection evaluated using FCM. (b) Apoptotic rates of BGC-823, MGC-803, and SGC-7901 cells at 24 h after transfection of miR-1273h-5p mimic. Compared to the negative control, the apoptosis ratio of miR-1273h-5p mimics was significantly increased. All data were expressed as M ± SD from three independent experiments compared with the negative control group, *P < 0.05, **P < 0.01.

3.3 Effect of miR-1273h-5p on the migration and invasion of GC cells

Cell migration and invasion were explored using the transwell assay, and the number of migratory and invasive cells was counted using a microscope (100× and 200×). Results indicated that the overexpression of miR-1273h-5p inhibited the migration of BGC-823 and SGC-7901 cells (Figure 4). In addition, the invasion of BGC-823, MGC-803, and SGC-7901 cells was also inhibited by overexpression of miR-1273h-5p compared to normal and negative control groups (Figure 5).

Figure 4 Effect of miR-1273h-5p on GC cell migration. (a and b) Effect of miR-1273h-5p on the migration of BGC-823 cells at 24 h after transfection determined by transwell assay. Compared to the negative control, the ratio of migration was significantly reduced in the miR-1273h-5p group. (c and d) Impact of miR-1273h-5p on the migration of MGC-803 cells at 24 h after transfection determined using transwell assay. (e and f) Impact of miR-1273h-5p on the migration of SGC-7901 cells at 24 h after transfection determined by transwell assay. The migratory ratio of the miR-1273h-5p group revealed significantly decreased contrast with negative control. Pictures of each group included two kinds of specifications with 200× used for statistics. Scale bars have been depicted. All data were expressed as M ± SD from three independent experiments when compared with the negative control group, **P < 0.01.
Figure 4

Effect of miR-1273h-5p on GC cell migration. (a and b) Effect of miR-1273h-5p on the migration of BGC-823 cells at 24 h after transfection determined by transwell assay. Compared to the negative control, the ratio of migration was significantly reduced in the miR-1273h-5p group. (c and d) Impact of miR-1273h-5p on the migration of MGC-803 cells at 24 h after transfection determined using transwell assay. (e and f) Impact of miR-1273h-5p on the migration of SGC-7901 cells at 24 h after transfection determined by transwell assay. The migratory ratio of the miR-1273h-5p group revealed significantly decreased contrast with negative control. Pictures of each group included two kinds of specifications with 200× used for statistics. Scale bars have been depicted. All data were expressed as M ± SD from three independent experiments when compared with the negative control group, **P < 0.01.

Figure 5 Effect of miR-1273h-5p on GC cell invasion. (a and b) Effect of miR-1273h-5p on the invasion of BGC-823 cells at 24 h after transfection determined by transwell assay. (c and d) Impact of miR-1273h-5p on the invasion of MGC-803 cells at 24 h after transfection determined by transwell assay. (e and f) Impact of miR-1273h-5p on the invasion of SGC-7901 cells at 24 h after transfection determined using transwell assay. The miR-1273h-5p group had a significant decrease in contrast with the negative group in three cell models. Pictures of each group included two kinds of specifications with 200× used for statistics. Scale bars have been depicted. All data were expressed as M ± SD from three independent experiments compared with the negative control group, **P < 0.01.
Figure 5

Effect of miR-1273h-5p on GC cell invasion. (a and b) Effect of miR-1273h-5p on the invasion of BGC-823 cells at 24 h after transfection determined by transwell assay. (c and d) Impact of miR-1273h-5p on the invasion of MGC-803 cells at 24 h after transfection determined by transwell assay. (e and f) Impact of miR-1273h-5p on the invasion of SGC-7901 cells at 24 h after transfection determined using transwell assay. The miR-1273h-5p group had a significant decrease in contrast with the negative group in three cell models. Pictures of each group included two kinds of specifications with 200× used for statistics. Scale bars have been depicted. All data were expressed as M ± SD from three independent experiments compared with the negative control group, **P < 0.01.

3.4 High expression of miR-1273h-5p downregulates CXCL12

Bioinformatics analysis was conducted using TargetScan and miRanda software, and CXCL12 was identified as a potential target gene (Figure 6a). And miR-1273h-5p negative control plasmid could not regulate the CXCL12 level (Figure 6b and d). However, overexpression of miR-1273h-5p could downregulate wild-type CXCL12 mRNA level, but could not downregulate mutant-type CXCL12 mRNA (in which binding site was mutated) level (Figure 6c and e).

Figure 6 Bioinformatics analysis of miR-1273h-5p and target gene correlation. (a) Potential targeting (binding) site of miR-1273h-5p on CXCL12 mRNA predicted using TargetScan and miRanda software. (b and d) After the combination of miR-1273h-5p-negative control plasmid with CXCL12 plasmids, including negative control, wide type, and mutation. (c and e) In comparison with negative control group, the RLU ratio of miR-1273h-5p mimic combined with CXCL12 wide-type plasmid significantly decreased. All transfection trials were conducted using the HKE293 cells (*P < 0.05).
Figure 6

Bioinformatics analysis of miR-1273h-5p and target gene correlation. (a) Potential targeting (binding) site of miR-1273h-5p on CXCL12 mRNA predicted using TargetScan and miRanda software. (b and d) After the combination of miR-1273h-5p-negative control plasmid with CXCL12 plasmids, including negative control, wide type, and mutation. (c and e) In comparison with negative control group, the RLU ratio of miR-1273h-5p mimic combined with CXCL12 wide-type plasmid significantly decreased. All transfection trials were conducted using the HKE293 cells (*P < 0.05).

3.5 Binding to the target gene CXCL12 in GC cells

The CXCL12 mRNA expression was dramatically downregulated in GC cells transfected with miR-1273h-5p mimics (Figure 7a). Similarly, the protein expression of CXCL12 was also obviously reduced (Figure 7b–h). These results suggested that miR-1273h-5p may play a biological role in down-regulating the expression of CXCL12.

Figure 7 Verification of target gene CXCL12 in GC cells. (a) The expression of CXCL12 at the mRNA level in BGC-823, MGC-803, and SGC-7901 cells following miR-1273h-5p mimic transfection was evaluated using RT-PCR. miR-1273h-5p mimic group revealed a significant decrease compared to the negative group in three GC cells. (b, d, and f) The expression of CXCL12 at the protein level in BGC-823, MGC-803, and SGC-7901 cells following miR-1273h-5p mimic transfection determined using Western blot. The expression of CXCL12 in mimics revealed a significant reduction of BGC-823 and SGC-7901cells by contrast with negative control. (c, e, and h) Protein electrophoretic bands of BGC-823, MGC-803, and SGC-7901 cells, respectively. All data were represented as M ± SD from three independent experiments compared with the negative control group, *P < 0.05, **P < 0.01.
Figure 7

Verification of target gene CXCL12 in GC cells. (a) The expression of CXCL12 at the mRNA level in BGC-823, MGC-803, and SGC-7901 cells following miR-1273h-5p mimic transfection was evaluated using RT-PCR. miR-1273h-5p mimic group revealed a significant decrease compared to the negative group in three GC cells. (b, d, and f) The expression of CXCL12 at the protein level in BGC-823, MGC-803, and SGC-7901 cells following miR-1273h-5p mimic transfection determined using Western blot. The expression of CXCL12 in mimics revealed a significant reduction of BGC-823 and SGC-7901cells by contrast with negative control. (c, e, and h) Protein electrophoretic bands of BGC-823, MGC-803, and SGC-7901 cells, respectively. All data were represented as M ± SD from three independent experiments compared with the negative control group, *P < 0.05, **P < 0.01.

3.6 In vivo validation

The xenograft tumor model in nude mice was established, and the volume and weight of tumor tissue were measured after 21 days of feeding. The tumor volume and weight of the miR-1273h-5p mimic group (n = 10) were significantly lower than those of the normal control group (n = 10) and negative control group (n = 10) (Figure 8a and b), and the miR-1273h-5p level was significantly overexpressed (Figure 8c). CXCL12 mRNA and protein were significantly lower in the miR-1273h-5p group compared to normal and negative control groups (Figure 8d–f).

Figure 8 Effect of miR-1273h-5p on SGC-7901 cell transplanted mice model. (a and b) Tumor volume and weight of cancer tissue among the normal control group, negative control group, and miR-1273h-5p group revealed significant reductions. (c and d) The expression of miR-1273h-5p and CXCL12 at the mRNA level in normal control, negative control, and the miR-1273h-5p transfected groups was evaluated using RT-PCR. In contrast with the negative group, the miR-1273h-5p group significantly increased. (e and f) The expression of CXCL12 at the protein level in three groups was determined by Western blotting analysis. The miR-1273h-5p group significantly decreased compared to the negative group. All data were represented as M ± SD from three independent experiments compared with the negative control group, *P < 0.05, **P < 0.01.
Figure 8

Effect of miR-1273h-5p on SGC-7901 cell transplanted mice model. (a and b) Tumor volume and weight of cancer tissue among the normal control group, negative control group, and miR-1273h-5p group revealed significant reductions. (c and d) The expression of miR-1273h-5p and CXCL12 at the mRNA level in normal control, negative control, and the miR-1273h-5p transfected groups was evaluated using RT-PCR. In contrast with the negative group, the miR-1273h-5p group significantly increased. (e and f) The expression of CXCL12 at the protein level in three groups was determined by Western blotting analysis. The miR-1273h-5p group significantly decreased compared to the negative group. All data were represented as M ± SD from three independent experiments compared with the negative control group, *P < 0.05, **P < 0.01.

4 Discussion

It is well known that the dysfunction of miRNAs is tightly correlated with the pathogenesis of different human tumors, thus indicating that miRNAs may function as oncogenes or tumor suppressors [25]. For example, the overexpression of miR-215 leads to the suppressed growth and penetration of breast cancer cells by targeting AKT1 [26]. The upregulated miR-223-3p enhances the cell proliferation, migration, and invasion in ovarian cancer by targeting SOX11 [27]. miRNA-3662 is a negative regulator of pancreatic ductal adenocarcinoma (PDAC) chemoresistance by constructing the PDAC subcutaneous xenograft tumor model [28]. Co-delivery of 5-FU and miR-34a(m) could achieve synergistic effects on tumor suppression in vitro and in vivo by enhancing anti-colorectal cancer (CRC) activity of 5-FU via silencing sirt1 expression and suppressing CRC cell migration by targeting CD44 [29].

In GC, many dysregulated miRNAs, such as miR-30b, miR-372, and miR-21, have been shown to be involved in the growth, apoptosis, migration, and penetration [30,31,32]. In our current work, miR-1273h-5p was lowly expressed in GC tissues and cell lines, reducing the level of miR-1273h-5p can promote the proliferation of GC cells, suggesting that miR-1273h-5p may play a tumor suppressor role in GC. If this hypothesis is correct, increasing the level of miR-1273h-5p may play a role in suppressing GC. After we exogenously increased intracellular miR-1273h-5p, the proliferation, invasion, and migration ability of GC cells, and the growth of transplanted tumors were significantly decreased, meanwhile the apoptosis of cells was increased, indicating the tumor suppressor function of miR-1273h-5p. These findings provide new clues for GC treatment.

miR-1273h-5p is a member of the miR-1273 family, and the expression of miR-1273 is frequently found in various kinds of diseases. miR-1273d and miR-1273g-3p have been associated with different types of cancers, such as progressive lymphoma, diffused melanoma neoplasm metastasis, neoplasm skin neoplasms, uterine, and cervical neoplasms [33]. Moreover, miR-1273g-3p is also significantly dysregulated in patients with chronic obstructive pulmonary disease [34]. The upregulation of miR-1273 was detected in the KrasG12D Pdx1-Cre pancreatic cancer mouse model compared with the control mice [35]. The downregulation of miR-1273 in early atherosclerotic plaque tissues has been confirmed, and the specific regulatory pattern of miRNAs in early atherosclerotic plaques may be useful in determining the formation and stability of plaques [36].

MiRNAs can modulate the translation and stability of their target messenger RNAs (mRNAs) by binding to complementary sequences of 3′-untranslational regions (3′-UTR) of the transcripts [37]. miRNA duplex was generated through a sophisticated biochemical process from the pre-miRNA. After integrating with RNA-induced silencing (RISC) complex, the duplex guided the RISC complex to the target mRNA aiming at a complementarily dependent process-regulating genes. The results of complement between “seed region” and target mRNA could lead to two consequences: related RISC’s degradation and translation repression [38].

By analyzing the binding sites and co-expression, we found that Chemokine 12 (CXCL12) has binding sites with miR-1273h-5p, and the expression is negatively correlated, which may be the target gene of miR-1273h-5p. Previous studies have found that CXCL12 can be regulated by miRNAs. miR-448 inhibits cell proliferation, migration, and invasion in ovarian cancer by targeting CXCL12 expression [39]. Some complementary binding sites between miR-455-5p and CXCL12 have been found, and a significant inverse correlation has been detected as well, indicating that miR-455-5p might suppress medullary thyroid cancer growth and metastasis by targeting CXCL12/CXCR4 signaling pathway [40]. In GC, miR-204-5p is discovered to target the 3′-UTR of CXCL12 as a tumor suppressor, regulating invasion and migration [41]. miR-23a-3p could modulate CXCL12-mediated angiogenesis to affect GC’s proliferation and migration [42]. The increasing expression of CXCL12 under the interaction of miR-141-3p and circDLG1 could promote GC progression and resistance to anti-PD-1-based therapy [43].

CXCL12 is also known as stromal cell-derived factor-1, a member of the CXC chemokine subfamily. It maintains tissue homeostasis in different physiological and pathological processes and participates in the survival and recruitment of immune cells [44,45,46]. Numerous investigations have shown that extracellular CXCL12 is overexpressed in different types of tumors and promotes the occurrence, invasion, and metastasis of tumors such as GC, CRC, breast cancer, and melanoma [47]. The combination of CXCL12 and CXCR4 can activate signaling pathways such as MAPK/ERK, PI3K/Akt/NF-κB, and c-Jun N-terminal kinase and regulate tumor progression [48,49]. Overexpression of CXCL12 can promote the growth of human breast cancer cells [50], exacerbating nasopharyngeal carcinoma cell migration and invasion by binding to its receptor CXCR4 [51].

In GC tissues, CXCL12/CXCR4, highly overexpressed, is tightly correlated with the metastasis of lymph nodes, higher tumor, node, metastasis staging, and poor prognosis [52,53]. CXCL12 can also promote the expressions of epidermal growth factor receptor ligands, such as amphiregulin and heparin-binding EGF-like growth factor, in GC cells leading to increased migration [54]. CXCL12 could also mediate the trafficking of normal and tumor cells by binding to CXCR7 [55], and the CXCL12/CXCR7 axis is involved in lymph node and liver metastasis of GC [56].

Collectively, miR-1273h-5p functions as a tumor suppressor gene and participates in the pathogenesis of GC. Low-expressed miR-1273h-5p in GC may relieve its inhibitory effect on CXCL12. In another aspect, overexpression of miR-1273h-5p could enhance the apoptosis of GC cells and suppress the cell growth and invasion, possibly by binding to 3′-UTR of CXCL12 mRNA so as to decrease the CXCL12 expression. Therefore, miR-1273h-5p may be a new therapeutic regimen for GC patients in the future.

tel: +86-10-83198855

  1. Funding information: This study was supported by National Natural Science Foundation of China (No. 81773778) and China Postdoctoral Science Foundation (2019M650775, 2020T130438)

  2. Author contributions: Xian-Zhe Dong and Yi-Chen Wang designed the experiment and wrote the manuscript; Ping Liu and Yuan Hu reviewed the manuscript for its intellectual content and revised the entire work; Xian-Zhe Dong, Yi-Chen Wang, Song Lu, Xiao-jiang Zhou, and Li Yang performed the histological assessments and evaluations; Lan Zhang reviewed the manuscript for its intellectual content. All authors have read and approved the final manuscript.

  3. Conflict of interest: The authors declare that they have no conflict of interest.

  4. Data availability statement: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Appendix

Figure A1 Firefly luciferase plasmids of target gene (CXCL12). (a) During the co-transfection process, experimental grouping has been completed, including miR-1273h-5p(negative con)-CXCL12(negative con), miR-1273h-5p(negative con)-CXCL12(wide type 1 or 2), miR-1273h-5p(negative con)-CXCL12(mutant 1 or 2), miR-1273h-5p(mimic)-CXCL12(negative con), miR-1273h-5p(mimic)-CXCL12(wide type 1 or 2), and miR-1273h-5p(mimic)-CXCL12(mutant 1 or 2). (b) Firefly luciferase negative control plasmids, which did not carry the gene sequence. (c) Base sequences of CXCL12 wild type 1 and mutation 1 and assembly sites with plasmid vectors. (d) Base sequences of CXCL12 wild type 2 and mutation 2 and assembly sites with plasmid vectors. The sequence of junction bases with miRNA is bold.
Figure A1

Firefly luciferase plasmids of target gene (CXCL12). (a) During the co-transfection process, experimental grouping has been completed, including miR-1273h-5p(negative con)-CXCL12(negative con), miR-1273h-5p(negative con)-CXCL12(wide type 1 or 2), miR-1273h-5p(negative con)-CXCL12(mutant 1 or 2), miR-1273h-5p(mimic)-CXCL12(negative con), miR-1273h-5p(mimic)-CXCL12(wide type 1 or 2), and miR-1273h-5p(mimic)-CXCL12(mutant 1 or 2). (b) Firefly luciferase negative control plasmids, which did not carry the gene sequence. (c) Base sequences of CXCL12 wild type 1 and mutation 1 and assembly sites with plasmid vectors. (d) Base sequences of CXCL12 wild type 2 and mutation 2 and assembly sites with plasmid vectors. The sequence of junction bases with miRNA is bold.

Figure A2 The expression of miR-1273h-5p after miR-1273h-5p mimics and inhibitor transfection. (a–c) The expressions of miR-1273h-5p after transplantation of miR-1273h-5p mimics into BGC-823, MGC-823 and SGC-7901 cells. (d–f) The expressions of miR-1273h-5p after transplantation of miR-1273h-5p inhibitor into BGC-823, MGC-823 and SGC-7901 cells. All data were represented as M ± SD, *P < 0.05,**P < 0.01.
Figure A2

The expression of miR-1273h-5p after miR-1273h-5p mimics and inhibitor transfection. (a–c) The expressions of miR-1273h-5p after transplantation of miR-1273h-5p mimics into BGC-823, MGC-823 and SGC-7901 cells. (d–f) The expressions of miR-1273h-5p after transplantation of miR-1273h-5p inhibitor into BGC-823, MGC-823 and SGC-7901 cells. All data were represented as M ± SD, *P < 0.05,**P < 0.01.

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Received: 2021-10-17
Revised: 2022-04-15
Accepted: 2022-04-28
Published Online: 2022-05-16

© 2022 Yi-Chen Wang et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  38. Cx43 upregulation in HUVECs under stretch via TGF-β1 and cytoskeletal network
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  40. Histopathologic findings on removed stomach after sleeve gastrectomy. Do they influence the outcome?
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  42. Optimal diagnosis of the skin cancer using a hybrid deep neural network and grasshopper optimization algorithm
  43. miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells
  44. Clinical value of SIRT1 as a prognostic biomarker in esophageal squamous cell carcinoma, a systematic meta-analysis
  45. circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8
  46. miR-22-5p regulates the self-renewal of spermatogonial stem cells by targeting EZH2
  47. hsa-miR-340-5p inhibits epithelial–mesenchymal transition in endometriosis by targeting MAP3K2 and inactivating MAPK/ERK signaling
  48. circ_0085296 inhibits the biological functions of trophoblast cells to promote the progression of preeclampsia via the miR-942-5p/THBS2 network
  49. TCD hemodynamics findings in the subacute phase of anterior circulation stroke patients treated with mechanical thrombectomy
  50. Development of a risk-stratification scoring system for predicting risk of breast cancer based on non-alcoholic fatty liver disease, non-alcoholic fatty pancreas disease, and uric acid
  51. Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway
  52. circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis
  53. Human amniotic fluid as a source of stem cells
  54. lncRNA NONRATT013819.2 promotes transforming growth factor-β1-induced myofibroblastic transition of hepatic stellate cells by miR24-3p/lox
  55. NORAD modulates miR-30c-5p-LDHA to protect lung endothelial cells damage
  56. Idiopathic pulmonary fibrosis telemedicine management during COVID-19 outbreak
  57. Risk factors for adverse drug reactions associated with clopidogrel therapy
  58. Serum zinc associated with immunity and inflammatory markers in Covid-19
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  60. LncRNA expression in idiopathic achalasia: New insight and preliminary exploration into pathogenesis
  61. Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway
  62. Moscatilin suppresses the inflammation from macrophages and T cells
  63. Zoledronate promotes ECM degradation and apoptosis via Wnt/β-catenin
  64. Epithelial-mesenchymal transition-related genes in coronary artery disease
  65. The effect evaluation of traditional vaginal surgery and transvaginal mesh surgery for severe pelvic organ prolapse: 5 years follow-up
  66. Repeated partial splenic artery embolization for hypersplenism improves platelet count
  67. Low expression of miR-27b in serum exosomes of non-small cell lung cancer facilitates its progression by affecting EGFR
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  70. The effect of tranexamic acid on the reduction of intraoperative and postoperative blood loss and thromboembolic risk in patients with hip fracture
  71. Isocitrate dehydrogenase 1 mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to ferroptosis
  72. Artemisinin protects against cerebral ischemia and reperfusion injury via inhibiting the NF-κB pathway
  73. A 16-gene signature associated with homologous recombination deficiency for prognosis prediction in patients with triple-negative breast cancer
  74. Lidocaine ameliorates chronic constriction injury-induced neuropathic pain through regulating M1/M2 microglia polarization
  75. MicroRNA 322-5p reduced neuronal inflammation via the TLR4/TRAF6/NF-κB axis in a rat epilepsy model
  76. miR-1273h-5p suppresses CXCL12 expression and inhibits gastric cancer cell invasion and metastasis
  77. Clinical characteristics of pneumonia patients of long course of illness infected with SARS-CoV-2
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  79. Linezolid for resistant Gram-positive bacterial infections in children under 12 years: A meta-analysis
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  81. Comprehensive analysis of molecular mechanism and a novel prognostic signature based on small nuclear RNA biomarkers in gastric cancer patients
  82. Smog and risk of maternal and fetal birth outcomes: A retrospective study in Baoding, China
  83. Let-7i-3p inhibits the cell cycle, proliferation, invasion, and migration of colorectal cancer cells via downregulating CCND1
  84. β2-Adrenergic receptor expression in subchondral bone of patients with varus knee osteoarthritis
  85. Possible impact of COVID-19 pandemic and lockdown on suicide behavior among patients in Southeast Serbia
  86. In vitro antimicrobial activity of ozonated oil in liposome eyedrop against multidrug-resistant bacteria
  87. Potential biomarkers for inflammatory response in acute lung injury
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  89. Antitumor activity of recombinant oncolytic vaccinia virus with human IL2
  90. ALKBH5 inhibits TNF-α-induced apoptosis of HUVECs through Bcl-2 pathway
  91. Risk prediction of cardiovascular disease using machine learning classifiers
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  93. Bioinformatics analysis reveals three key genes and four survival genes associated with youth-onset NSCLC
  94. Identification of autophagy-related biomarkers in patients with pulmonary arterial hypertension based on bioinformatics analysis
  95. Protective effects of glaucocalyxin A on the airway of asthmatic mice
  96. Overexpression of miR-100-5p inhibits papillary thyroid cancer progression via targeting FZD8
  97. Bioinformatics-based analysis of SUMOylation-related genes in hepatocellular carcinoma reveals a role of upregulated SAE1 in promoting cell proliferation
  98. Effectiveness and clinical benefits of new anti-diabetic drugs: A real life experience
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  108. Protective effect of ghrelin on intestinal I/R injury in rats
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  114. Endothelial cell-specific molecule 1 (ESM1) promoted by transcription factor SPI1 acts as an oncogene to modulate the malignant phenotype of endometrial cancer
  115. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition
  116. Visfatin is negatively associated with coronary artery lesions in subjects with impaired fasting glucose
  117. Treatment and outcomes of mechanical complications of acute myocardial infarction during the Covid-19 era: A comparison with the pre-Covid-19 period. A systematic review and meta-analysis
  118. Neonatal stroke surveillance study protocol in the United Kingdom and Republic of Ireland
  119. Oncogenic role of TWF2 in human tumors: A pan-cancer analysis
  120. Mean corpuscular hemoglobin predicts the length of hospital stay independent of severity classification in patients with acute pancreatitis
  121. Association of gallstone and polymorphisms of UGT1A1*27 and UGT1A1*28 in patients with hepatitis B virus-related liver failure
  122. TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
  123. Antisense lncRNA PCNA-AS1 promotes esophageal squamous cell carcinoma progression through the miR-2467-3p/PCNA axis
  124. NK-cell dysfunction of acute myeloid leukemia in relation to the renin–angiotensin system and neurotransmitter genes
  125. The effect of dilution with glucose and prolonged injection time on dexamethasone-induced perineal irritation – A randomized controlled trial
  126. miR-146-5p restrains calcification of vascular smooth muscle cells by suppressing TRAF6
  127. Role of lncRNA MIAT/miR-361-3p/CCAR2 in prostate cancer cells
  128. lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2
  129. Noninvasive diagnosis of AIH/PBC overlap syndrome based on prediction models
  130. lncRNA FAM230B is highly expressed in colorectal cancer and suppresses the maturation of miR-1182 to increase cell proliferation
  131. circ-LIMK1 regulates cisplatin resistance in lung adenocarcinoma by targeting miR-512-5p/HMGA1 axis
  132. LncRNA SNHG3 promoted cell proliferation, migration, and metastasis of esophageal squamous cell carcinoma via regulating miR-151a-3p/PFN2 axis
  133. Risk perception and affective state on work exhaustion in obstetrics during the COVID-19 pandemic
  134. lncRNA-AC130710/miR-129-5p/mGluR1 axis promote migration and invasion by activating PKCα-MAPK signal pathway in melanoma
  135. SNRPB promotes cell cycle progression in thyroid carcinoma via inhibiting p53
  136. Xylooligosaccharides and aerobic training regulate metabolism and behavior in rats with streptozotocin-induced type 1 diabetes
  137. Serpin family A member 1 is an oncogene in glioma and its translation is enhanced by NAD(P)H quinone dehydrogenase 1 through RNA-binding activity
  138. Silencing of CPSF7 inhibits the proliferation, migration, and invasion of lung adenocarcinoma cells by blocking the AKT/mTOR signaling pathway
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  141. Identification of a novel necroptosis-associated miRNA signature for predicting the prognosis in head and neck squamous cell carcinoma
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  144. Longitudinal analysis of factors related to Helicobacter pylori infection in Chinese adults
  145. HOXA10 enhances cell proliferation and suppresses apoptosis in esophageal cancer via activating p38/ERK signaling pathway
  146. Meta-analysis of early-life antibiotic use and allergic rhinitis
  147. Marital status and its correlation with age, race, and gender in prognosis of tonsil squamous cell carcinomas
  148. HPV16 E6E7 up-regulates KIF2A expression by activating JNK/c-Jun signal, is beneficial to migration and invasion of cervical cancer cells
  149. Amino acid profiles in the tissue and serum of patients with liver cancer
  150. Pain in critically ill COVID-19 patients: An Italian retrospective study
  151. Immunohistochemical distribution of Bcl-2 and p53 apoptotic markers in acetamiprid-induced nephrotoxicity
  152. Estradiol pretreatment in GnRH antagonist protocol for IVF/ICSI treatment
  153. Long non-coding RNAs LINC00689 inhibits the apoptosis of human nucleus pulposus cells via miR-3127-5p/ATG7 axis-mediated autophagy
  154. The relationship between oxygen therapy, drug therapy, and COVID-19 mortality
  155. Monitoring hypertensive disorders in pregnancy to prevent preeclampsia in pregnant women of advanced maternal age: Trial mimicking with retrospective data
  156. SETD1A promotes the proliferation and glycolysis of nasopharyngeal carcinoma cells by activating the PI3K/Akt pathway
  157. The role of Shunaoxin pills in the treatment of chronic cerebral hypoperfusion and its main pharmacodynamic components
  158. TET3 governs malignant behaviors and unfavorable prognosis of esophageal squamous cell carcinoma by activating the PI3K/AKT/GSK3β/β-catenin pathway
  159. Associations between morphokinetic parameters of temporary-arrest embryos and the clinical prognosis in FET cycles
  160. Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis
  161. The incidence of bronchiectasis in chronic obstructive pulmonary disease
  162. Integrated bioinformatics analysis shows integrin alpha 3 is a prognostic biomarker for pancreatic cancer
  163. Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway
  164. Comparison of hospitalized patients with severe pneumonia caused by COVID-19 and influenza A (H7N9 and H1N1): A retrospective study from a designated hospital
  165. lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1
  166. Pathological characteristics of liver injury induced by N,N-dimethylformamide: From humans to animal models
  167. lncRNA ELFN1-AS1 enhances the progression of colon cancer by targeting miR-4270 to upregulate AURKB
  168. DARS-AS1 modulates cell proliferation and migration of gastric cancer cells by regulating miR-330-3p/NAT10 axis
  169. Dezocine inhibits cell proliferation, migration, and invasion by targeting CRABP2 in ovarian cancer
  170. MGST1 alleviates the oxidative stress of trophoblast cells induced by hypoxia/reoxygenation and promotes cell proliferation, migration, and invasion by activating the PI3K/AKT/mTOR pathway
  171. Bifidobacterium lactis Probio-M8 ameliorated the symptoms of type 2 diabetes mellitus mice by changing ileum FXR-CYP7A1
  172. circRNA DENND1B inhibits tumorigenicity of clear cell renal cell carcinoma via miR-122-5p/TIMP2 axis
  173. EphA3 targeted by miR-3666 contributes to melanoma malignancy via activating ERK1/2 and p38 MAPK pathways
  174. Pacemakers and methylprednisolone pulse therapy in immune-related myocarditis concomitant with complete heart block
  175. miRNA-130a-3p targets sphingosine-1-phosphate receptor 1 to activate the microglial and astrocytes and to promote neural injury under the high glucose condition
  176. Review Articles
  177. Current management of cancer pain in Italy: Expert opinion paper
  178. Hearing loss and brain disorders: A review of multiple pathologies
  179. The rationale for using low-molecular weight heparin in the therapy of symptomatic COVID-19 patients
  180. Amyotrophic lateral sclerosis and delayed onset muscle soreness in light of the impaired blink and stretch reflexes – watch out for Piezo2
  181. Interleukin-35 in autoimmune dermatoses: Current concepts
  182. Recent discoveries in microbiota dysbiosis, cholangiocytic factors, and models for studying the pathogenesis of primary sclerosing cholangitis
  183. Advantages of ketamine in pediatric anesthesia
  184. Congenital adrenal hyperplasia. Role of dentist in early diagnosis
  185. Migraine management: Non-pharmacological points for patients and health care professionals
  186. Atherogenic index of plasma and coronary artery disease: A systematic review
  187. Physiological and modulatory role of thioredoxins in the cellular function
  188. Case Reports
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  190. A case of successful pembrolizumab monotherapy in a patient with advanced lung adenocarcinoma: Use of multiple biomarkers in combination for clinical practice
  191. Unusual neurological manifestations of bilateral medial medullary infarction: A case report
  192. Atypical symptoms of malignant hyperthermia: A rare causative mutation in the RYR1 gene
  193. A case report of dermatomyositis with the missed diagnosis of non-small cell lung cancer and concurrence of pulmonary tuberculosis
  194. A rare case of endometrial polyp complicated with uterine inversion: A case report and clinical management
  195. Spontaneous rupturing of splenic artery aneurysm: Another reason for fatal syncope and shock (Case report and literature review)
  196. Fungal infection mimicking COVID-19 infection – A case report
  197. Concurrent aspergillosis and cystic pulmonary metastases in a patient with tongue squamous cell carcinoma
  198. Paraganglioma-induced inverted takotsubo-like cardiomyopathy leading to cardiogenic shock successfully treated with extracorporeal membrane oxygenation
  199. Lineage switch from lymphoma to myeloid neoplasms: First case series from a single institution
  200. Trismus during tracheal extubation as a complication of general anaesthesia – A case report
  201. Simultaneous treatment of a pubovesical fistula and lymph node metastasis secondary to multimodal treatment for prostate cancer: Case report and review of the literature
  202. Two case reports of skin vasculitis following the COVID-19 immunization
  203. Ureteroiliac fistula after oncological surgery: Case report and review of the literature
  204. Synchronous triple primary malignant tumours in the bladder, prostate, and lung harbouring TP53 and MEK1 mutations accompanied with severe cardiovascular diseases: A case report
  205. Huge mucinous cystic neoplasms with adhesion to the left colon: A case report and literature review
  206. Commentary
  207. Commentary on “Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma”
  208. Rapid Communication
  209. COVID-19 fear, post-traumatic stress, growth, and the role of resilience
  210. Erratum
  211. Erratum to “Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway”
  212. Erratum to “Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study”
  213. Erratum to “lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2”
  214. Retraction
  215. Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
  216. Retraction to “miR-519d downregulates LEP expression to inhibit preeclampsia development”
  217. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part II
  218. Usefulness of close surveillance for rectal cancer patients after neoadjuvant chemoradiotherapy
https://doi.org/10.1515/med-2022-0486
Keywords for this article
gastric cancer; miR-1273h-5p; proliferation; apoptosis; migration; invasion
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. AMBRA1 attenuates the proliferation of uveal melanoma cells
  3. A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma
  4. Differences in complications between hepatitis B-related cirrhosis and alcohol-related cirrhosis
  5. Effect of gestational diabetes mellitus on lipid profile: A systematic review and meta-analysis
  6. Long noncoding RNA NR2F1-AS1 stimulates the tumorigenic behavior of non-small cell lung cancer cells by sponging miR-363-3p to increase SOX4
  7. Promising novel biomarkers and candidate small-molecule drugs for lung adenocarcinoma: Evidence from bioinformatics analysis of high-throughput data
  8. Plasmapheresis: Is it a potential alternative treatment for chronic urticaria?
  9. The biomarkers of key miRNAs and gene targets associated with extranodal NK/T-cell lymphoma
  10. Gene signature to predict prognostic survival of hepatocellular carcinoma
  11. Effects of miRNA-199a-5p on cell proliferation and apoptosis of uterine leiomyoma by targeting MED12
  12. Does diabetes affect paraneoplastic thrombocytosis in colorectal cancer?
  13. Is there any effect on imprinted genes H19, PEG3, and SNRPN during AOA?
  14. Leptin and PCSK9 concentrations are associated with vascular endothelial cytokines in patients with stable coronary heart disease
  15. Pericentric inversion of chromosome 6 and male fertility problems
  16. Staple line reinforcement with nebulized cyanoacrylate glue in laparoscopic sleeve gastrectomy: A propensity score-matched study
  17. Retrospective analysis of crescent score in clinical prognosis of IgA nephropathy
  18. Expression of DNM3 is associated with good outcome in colorectal cancer
  19. Activation of SphK2 contributes to adipocyte-induced EOC cell proliferation
  20. CRRT influences PICCO measurements in febrile critically ill patients
  21. SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis
  22. lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells
  23. circ_AKT3 knockdown suppresses cisplatin resistance in gastric cancer
  24. Prognostic value of nicotinamide N-methyltransferase in human cancers: Evidence from a meta-analysis and database validation
  25. GPC2 deficiency inhibits cell growth and metastasis in colon adenocarcinoma
  26. A pan-cancer analysis of the oncogenic role of Holliday junction recognition protein in human tumors
  27. Radiation increases COL1A1, COL3A1, and COL1A2 expression in breast cancer
  28. Association between preventable risk factors and metabolic syndrome
  29. miR-29c-5p knockdown reduces inflammation and blood–brain barrier disruption by upregulating LRP6
  30. Cardiac contractility modulation ameliorates myocardial metabolic remodeling in a rabbit model of chronic heart failure through activation of AMPK and PPAR-α pathway
  31. Quercitrin protects human bronchial epithelial cells from oxidative damage
  32. Smurf2 suppresses the metastasis of hepatocellular carcinoma via ubiquitin degradation of Smad2
  33. circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury
  34. Sonoclot’s usefulness in prediction of cardiopulmonary arrest prognosis: A proof of concept study
  35. Four drug metabolism-related subgroups of pancreatic adenocarcinoma in prognosis, immune infiltration, and gene mutation
  36. Decreased expression of miR-195 mediated by hypermethylation promotes osteosarcoma
  37. LMO3 promotes proliferation and metastasis of papillary thyroid carcinoma cells by regulating LIMK1-mediated cofilin and the β-catenin pathway
  38. Cx43 upregulation in HUVECs under stretch via TGF-β1 and cytoskeletal network
  39. Evaluation of menstrual irregularities after COVID-19 vaccination: Results of the MECOVAC survey
  40. Histopathologic findings on removed stomach after sleeve gastrectomy. Do they influence the outcome?
  41. Analysis of the expression and prognostic value of MT1-MMP, β1-integrin and YAP1 in glioma
  42. Optimal diagnosis of the skin cancer using a hybrid deep neural network and grasshopper optimization algorithm
  43. miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells
  44. Clinical value of SIRT1 as a prognostic biomarker in esophageal squamous cell carcinoma, a systematic meta-analysis
  45. circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8
  46. miR-22-5p regulates the self-renewal of spermatogonial stem cells by targeting EZH2
  47. hsa-miR-340-5p inhibits epithelial–mesenchymal transition in endometriosis by targeting MAP3K2 and inactivating MAPK/ERK signaling
  48. circ_0085296 inhibits the biological functions of trophoblast cells to promote the progression of preeclampsia via the miR-942-5p/THBS2 network
  49. TCD hemodynamics findings in the subacute phase of anterior circulation stroke patients treated with mechanical thrombectomy
  50. Development of a risk-stratification scoring system for predicting risk of breast cancer based on non-alcoholic fatty liver disease, non-alcoholic fatty pancreas disease, and uric acid
  51. Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway
  52. circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis
  53. Human amniotic fluid as a source of stem cells
  54. lncRNA NONRATT013819.2 promotes transforming growth factor-β1-induced myofibroblastic transition of hepatic stellate cells by miR24-3p/lox
  55. NORAD modulates miR-30c-5p-LDHA to protect lung endothelial cells damage
  56. Idiopathic pulmonary fibrosis telemedicine management during COVID-19 outbreak
  57. Risk factors for adverse drug reactions associated with clopidogrel therapy
  58. Serum zinc associated with immunity and inflammatory markers in Covid-19
  59. The relationship between night shift work and breast cancer incidence: A systematic review and meta-analysis of observational studies
  60. LncRNA expression in idiopathic achalasia: New insight and preliminary exploration into pathogenesis
  61. Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway
  62. Moscatilin suppresses the inflammation from macrophages and T cells
  63. Zoledronate promotes ECM degradation and apoptosis via Wnt/β-catenin
  64. Epithelial-mesenchymal transition-related genes in coronary artery disease
  65. The effect evaluation of traditional vaginal surgery and transvaginal mesh surgery for severe pelvic organ prolapse: 5 years follow-up
  66. Repeated partial splenic artery embolization for hypersplenism improves platelet count
  67. Low expression of miR-27b in serum exosomes of non-small cell lung cancer facilitates its progression by affecting EGFR
  68. Exosomal hsa_circ_0000519 modulates the NSCLC cell growth and metastasis via miR-1258/RHOV axis
  69. miR-455-5p enhances 5-fluorouracil sensitivity in colorectal cancer cells by targeting PIK3R1 and DEPDC1
  70. The effect of tranexamic acid on the reduction of intraoperative and postoperative blood loss and thromboembolic risk in patients with hip fracture
  71. Isocitrate dehydrogenase 1 mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to ferroptosis
  72. Artemisinin protects against cerebral ischemia and reperfusion injury via inhibiting the NF-κB pathway
  73. A 16-gene signature associated with homologous recombination deficiency for prognosis prediction in patients with triple-negative breast cancer
  74. Lidocaine ameliorates chronic constriction injury-induced neuropathic pain through regulating M1/M2 microglia polarization
  75. MicroRNA 322-5p reduced neuronal inflammation via the TLR4/TRAF6/NF-κB axis in a rat epilepsy model
  76. miR-1273h-5p suppresses CXCL12 expression and inhibits gastric cancer cell invasion and metastasis
  77. Clinical characteristics of pneumonia patients of long course of illness infected with SARS-CoV-2
  78. circRNF20 aggravates the malignancy of retinoblastoma depending on the regulation of miR-132-3p/PAX6 axis
  79. Linezolid for resistant Gram-positive bacterial infections in children under 12 years: A meta-analysis
  80. Rack1 regulates pro-inflammatory cytokines by NF-κB in diabetic nephropathy
  81. Comprehensive analysis of molecular mechanism and a novel prognostic signature based on small nuclear RNA biomarkers in gastric cancer patients
  82. Smog and risk of maternal and fetal birth outcomes: A retrospective study in Baoding, China
  83. Let-7i-3p inhibits the cell cycle, proliferation, invasion, and migration of colorectal cancer cells via downregulating CCND1
  84. β2-Adrenergic receptor expression in subchondral bone of patients with varus knee osteoarthritis
  85. Possible impact of COVID-19 pandemic and lockdown on suicide behavior among patients in Southeast Serbia
  86. In vitro antimicrobial activity of ozonated oil in liposome eyedrop against multidrug-resistant bacteria
  87. Potential biomarkers for inflammatory response in acute lung injury
  88. A low serum uric acid concentration predicts a poor prognosis in adult patients with candidemia
  89. Antitumor activity of recombinant oncolytic vaccinia virus with human IL2
  90. ALKBH5 inhibits TNF-α-induced apoptosis of HUVECs through Bcl-2 pathway
  91. Risk prediction of cardiovascular disease using machine learning classifiers
  92. Value of ultrasonography parameters in diagnosing polycystic ovary syndrome
  93. Bioinformatics analysis reveals three key genes and four survival genes associated with youth-onset NSCLC
  94. Identification of autophagy-related biomarkers in patients with pulmonary arterial hypertension based on bioinformatics analysis
  95. Protective effects of glaucocalyxin A on the airway of asthmatic mice
  96. Overexpression of miR-100-5p inhibits papillary thyroid cancer progression via targeting FZD8
  97. Bioinformatics-based analysis of SUMOylation-related genes in hepatocellular carcinoma reveals a role of upregulated SAE1 in promoting cell proliferation
  98. Effectiveness and clinical benefits of new anti-diabetic drugs: A real life experience
  99. Identification of osteoporosis based on gene biomarkers using support vector machine
  100. Tanshinone IIA reverses oxaliplatin resistance in colorectal cancer through microRNA-30b-5p/AVEN axis
  101. miR-212-5p inhibits nasopharyngeal carcinoma progression by targeting METTL3
  102. Association of ST-T changes with all-cause mortality among patients with peripheral T-cell lymphomas
  103. LINC00665/miRNAs axis-mediated collagen type XI alpha 1 correlates with immune infiltration and malignant phenotypes in lung adenocarcinoma
  104. The perinatal factors that influence the excretion of fecal calprotectin in premature-born children
  105. Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study
  106. Does the use of 3D-printed cones give a chance to postpone the use of megaprostheses in patients with large bone defects in the knee joint?
  107. lncRNA HAGLR modulates myocardial ischemia–reperfusion injury in mice through regulating miR-133a-3p/MAPK1 axis
  108. Protective effect of ghrelin on intestinal I/R injury in rats
  109. In vivo knee kinematics of an innovative prosthesis design
  110. Relationship between the height of fibular head and the incidence and severity of knee osteoarthritis
  111. lncRNA WT1-AS attenuates hypoxia/ischemia-induced neuronal injury during cerebral ischemic stroke via miR-186-5p/XIAP axis
  112. Correlation of cardiac troponin T and APACHE III score with all-cause in-hospital mortality in critically ill patients with acute pulmonary embolism
  113. LncRNA LINC01857 reduces metastasis and angiogenesis in breast cancer cells via regulating miR-2052/CENPQ axis
  114. Endothelial cell-specific molecule 1 (ESM1) promoted by transcription factor SPI1 acts as an oncogene to modulate the malignant phenotype of endometrial cancer
  115. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition
  116. Visfatin is negatively associated with coronary artery lesions in subjects with impaired fasting glucose
  117. Treatment and outcomes of mechanical complications of acute myocardial infarction during the Covid-19 era: A comparison with the pre-Covid-19 period. A systematic review and meta-analysis
  118. Neonatal stroke surveillance study protocol in the United Kingdom and Republic of Ireland
  119. Oncogenic role of TWF2 in human tumors: A pan-cancer analysis
  120. Mean corpuscular hemoglobin predicts the length of hospital stay independent of severity classification in patients with acute pancreatitis
  121. Association of gallstone and polymorphisms of UGT1A1*27 and UGT1A1*28 in patients with hepatitis B virus-related liver failure
  122. TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
  123. Antisense lncRNA PCNA-AS1 promotes esophageal squamous cell carcinoma progression through the miR-2467-3p/PCNA axis
  124. NK-cell dysfunction of acute myeloid leukemia in relation to the renin–angiotensin system and neurotransmitter genes
  125. The effect of dilution with glucose and prolonged injection time on dexamethasone-induced perineal irritation – A randomized controlled trial
  126. miR-146-5p restrains calcification of vascular smooth muscle cells by suppressing TRAF6
  127. Role of lncRNA MIAT/miR-361-3p/CCAR2 in prostate cancer cells
  128. lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2
  129. Noninvasive diagnosis of AIH/PBC overlap syndrome based on prediction models
  130. lncRNA FAM230B is highly expressed in colorectal cancer and suppresses the maturation of miR-1182 to increase cell proliferation
  131. circ-LIMK1 regulates cisplatin resistance in lung adenocarcinoma by targeting miR-512-5p/HMGA1 axis
  132. LncRNA SNHG3 promoted cell proliferation, migration, and metastasis of esophageal squamous cell carcinoma via regulating miR-151a-3p/PFN2 axis
  133. Risk perception and affective state on work exhaustion in obstetrics during the COVID-19 pandemic
  134. lncRNA-AC130710/miR-129-5p/mGluR1 axis promote migration and invasion by activating PKCα-MAPK signal pathway in melanoma
  135. SNRPB promotes cell cycle progression in thyroid carcinoma via inhibiting p53
  136. Xylooligosaccharides and aerobic training regulate metabolism and behavior in rats with streptozotocin-induced type 1 diabetes
  137. Serpin family A member 1 is an oncogene in glioma and its translation is enhanced by NAD(P)H quinone dehydrogenase 1 through RNA-binding activity
  138. Silencing of CPSF7 inhibits the proliferation, migration, and invasion of lung adenocarcinoma cells by blocking the AKT/mTOR signaling pathway
  139. Ultrasound-guided lumbar plexus block versus transversus abdominis plane block for analgesia in children with hip dislocation: A double-blind, randomized trial
  140. Relationship of plasma MBP and 8-oxo-dG with brain damage in preterm
  141. Identification of a novel necroptosis-associated miRNA signature for predicting the prognosis in head and neck squamous cell carcinoma
  142. Delayed femoral vein ligation reduces operative time and blood loss during hip disarticulation in patients with extremity tumors
  143. The expression of ASAP3 and NOTCH3 and the clinicopathological characteristics of adult glioma patients
  144. Longitudinal analysis of factors related to Helicobacter pylori infection in Chinese adults
  145. HOXA10 enhances cell proliferation and suppresses apoptosis in esophageal cancer via activating p38/ERK signaling pathway
  146. Meta-analysis of early-life antibiotic use and allergic rhinitis
  147. Marital status and its correlation with age, race, and gender in prognosis of tonsil squamous cell carcinomas
  148. HPV16 E6E7 up-regulates KIF2A expression by activating JNK/c-Jun signal, is beneficial to migration and invasion of cervical cancer cells
  149. Amino acid profiles in the tissue and serum of patients with liver cancer
  150. Pain in critically ill COVID-19 patients: An Italian retrospective study
  151. Immunohistochemical distribution of Bcl-2 and p53 apoptotic markers in acetamiprid-induced nephrotoxicity
  152. Estradiol pretreatment in GnRH antagonist protocol for IVF/ICSI treatment
  153. Long non-coding RNAs LINC00689 inhibits the apoptosis of human nucleus pulposus cells via miR-3127-5p/ATG7 axis-mediated autophagy
  154. The relationship between oxygen therapy, drug therapy, and COVID-19 mortality
  155. Monitoring hypertensive disorders in pregnancy to prevent preeclampsia in pregnant women of advanced maternal age: Trial mimicking with retrospective data
  156. SETD1A promotes the proliferation and glycolysis of nasopharyngeal carcinoma cells by activating the PI3K/Akt pathway
  157. The role of Shunaoxin pills in the treatment of chronic cerebral hypoperfusion and its main pharmacodynamic components
  158. TET3 governs malignant behaviors and unfavorable prognosis of esophageal squamous cell carcinoma by activating the PI3K/AKT/GSK3β/β-catenin pathway
  159. Associations between morphokinetic parameters of temporary-arrest embryos and the clinical prognosis in FET cycles
  160. Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis
  161. The incidence of bronchiectasis in chronic obstructive pulmonary disease
  162. Integrated bioinformatics analysis shows integrin alpha 3 is a prognostic biomarker for pancreatic cancer
  163. Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway
  164. Comparison of hospitalized patients with severe pneumonia caused by COVID-19 and influenza A (H7N9 and H1N1): A retrospective study from a designated hospital
  165. lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1
  166. Pathological characteristics of liver injury induced by N,N-dimethylformamide: From humans to animal models
  167. lncRNA ELFN1-AS1 enhances the progression of colon cancer by targeting miR-4270 to upregulate AURKB
  168. DARS-AS1 modulates cell proliferation and migration of gastric cancer cells by regulating miR-330-3p/NAT10 axis
  169. Dezocine inhibits cell proliferation, migration, and invasion by targeting CRABP2 in ovarian cancer
  170. MGST1 alleviates the oxidative stress of trophoblast cells induced by hypoxia/reoxygenation and promotes cell proliferation, migration, and invasion by activating the PI3K/AKT/mTOR pathway
  171. Bifidobacterium lactis Probio-M8 ameliorated the symptoms of type 2 diabetes mellitus mice by changing ileum FXR-CYP7A1
  172. circRNA DENND1B inhibits tumorigenicity of clear cell renal cell carcinoma via miR-122-5p/TIMP2 axis
  173. EphA3 targeted by miR-3666 contributes to melanoma malignancy via activating ERK1/2 and p38 MAPK pathways
  174. Pacemakers and methylprednisolone pulse therapy in immune-related myocarditis concomitant with complete heart block
  175. miRNA-130a-3p targets sphingosine-1-phosphate receptor 1 to activate the microglial and astrocytes and to promote neural injury under the high glucose condition
  176. Review Articles
  177. Current management of cancer pain in Italy: Expert opinion paper
  178. Hearing loss and brain disorders: A review of multiple pathologies
  179. The rationale for using low-molecular weight heparin in the therapy of symptomatic COVID-19 patients
  180. Amyotrophic lateral sclerosis and delayed onset muscle soreness in light of the impaired blink and stretch reflexes – watch out for Piezo2
  181. Interleukin-35 in autoimmune dermatoses: Current concepts
  182. Recent discoveries in microbiota dysbiosis, cholangiocytic factors, and models for studying the pathogenesis of primary sclerosing cholangitis
  183. Advantages of ketamine in pediatric anesthesia
  184. Congenital adrenal hyperplasia. Role of dentist in early diagnosis
  185. Migraine management: Non-pharmacological points for patients and health care professionals
  186. Atherogenic index of plasma and coronary artery disease: A systematic review
  187. Physiological and modulatory role of thioredoxins in the cellular function
  188. Case Reports
  189. Intrauterine Bakri balloon tamponade plus cervical cerclage for the prevention and treatment of postpartum haemorrhage in late pregnancy complicated with acute aortic dissection: Case series
  190. A case of successful pembrolizumab monotherapy in a patient with advanced lung adenocarcinoma: Use of multiple biomarkers in combination for clinical practice
  191. Unusual neurological manifestations of bilateral medial medullary infarction: A case report
  192. Atypical symptoms of malignant hyperthermia: A rare causative mutation in the RYR1 gene
  193. A case report of dermatomyositis with the missed diagnosis of non-small cell lung cancer and concurrence of pulmonary tuberculosis
  194. A rare case of endometrial polyp complicated with uterine inversion: A case report and clinical management
  195. Spontaneous rupturing of splenic artery aneurysm: Another reason for fatal syncope and shock (Case report and literature review)
  196. Fungal infection mimicking COVID-19 infection – A case report
  197. Concurrent aspergillosis and cystic pulmonary metastases in a patient with tongue squamous cell carcinoma
  198. Paraganglioma-induced inverted takotsubo-like cardiomyopathy leading to cardiogenic shock successfully treated with extracorporeal membrane oxygenation
  199. Lineage switch from lymphoma to myeloid neoplasms: First case series from a single institution
  200. Trismus during tracheal extubation as a complication of general anaesthesia – A case report
  201. Simultaneous treatment of a pubovesical fistula and lymph node metastasis secondary to multimodal treatment for prostate cancer: Case report and review of the literature
  202. Two case reports of skin vasculitis following the COVID-19 immunization
  203. Ureteroiliac fistula after oncological surgery: Case report and review of the literature
  204. Synchronous triple primary malignant tumours in the bladder, prostate, and lung harbouring TP53 and MEK1 mutations accompanied with severe cardiovascular diseases: A case report
  205. Huge mucinous cystic neoplasms with adhesion to the left colon: A case report and literature review
  206. Commentary
  207. Commentary on “Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma”
  208. Rapid Communication
  209. COVID-19 fear, post-traumatic stress, growth, and the role of resilience
  210. Erratum
  211. Erratum to “Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway”
  212. Erratum to “Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study”
  213. Erratum to “lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2”
  214. Retraction
  215. Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
  216. Retraction to “miR-519d downregulates LEP expression to inhibit preeclampsia development”
  217. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part II
  218. Usefulness of close surveillance for rectal cancer patients after neoadjuvant chemoradiotherapy
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