Home Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis
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Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis

  • Qun Qiu and Juan Tan EMAIL logo
Published/Copyright: December 6, 2022
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Open Medicine
From the journal Open Medicine Volume 17 Issue 1

Abstract

This study aimed to determine the role of long noncoding RNA (lncRNA) WT1 antisense RNA (WT1-AS) in the occurrence and progression of preeclampsia (PE) and to determine the underlying molecular mechanisms. The associations between WT1-AS and microRNA (miR)-186-5p, and miR-186-5p and cell adhesion molecule 2 (CADM2) were predicted using StarBase software and verified via dual-luciferase assays. To explore the role of the human chorionic trophoblast line HTR-8/SVneo, gene (WT1-AS/miR-186-5p) gain/loss of function experiments were performed. Qualitative reverse transcription-polymerase chain reaction (RT-PCR) analysis was used to evaluate transfection efficiency. Cell proliferation, apoptosis, cell migration, and invasion were assessed using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry, and transwell analysis, respectively. Moreover, CADM2 protein expression was measured by western blotting. The results indicated that overexpression of WT1-AS inhibited cell viability, migration, and invasion, and induced apoptosis in HTR-8/SVneo cells. We observed that miR-186a-5p directly targeted WT1-AS, and miR-186a-5p knockdown reversed the effects of WT1-AS knockdown in HTR-8/SVneo cells. Binding sites were found between miR-186-5p and CADM2, and CADM2-overexpression reversed the influence of miR-186-5p mimic on HTR-8/SVneo cells. In summary, our findings demonstrated that lncRNA WT1-AS participates in PE by regulating the proliferation and invasion of placental trophoblasts, through the miR-186-5p/CADM2 axis.

Keywords: preeclampsia; placental trophoblasts; WT1 antisense RNA; microRNA-186-5p/cell adhesion molecule 2 axis

1 Introduction

Preeclampsia (PE), a disease that affects approximately 5% of all pregnancies, is one of the main causes of maternal morbidity worldwide [1,2]. PE is divided into mild and severe forms. In mild PE, pregnant women have high blood pressure and persistently increased proteinuria [3]. In addition to high blood pressure, severe PE symptoms include damage to other organs, including eclampsia, HELLP (hemolysis, elevated liver enzymes, thrombocytopenia) syndrome, liver damage, heart failure, abnormal kidney function, and fetal growth restriction [4,5,6]. A previous study demonstrated that abnormal placental development in early pregnancy could be a vital factor in the development of PE [7]. However, the pathogenesis of PE remains unclear.

Abnormal placental function, impaired trophoblast invasion, abnormal spiral artery remodeling, endothelial dysfunction, and promoted trophoblast apoptosis are associated with PE pathogenesis [8]. Among these, trophoblast behavior disorder is considered vital in the development of PE; thus, understanding its molecular mechanism can help develop novel treatment methods for PE [9]. Previous reports have demonstrated that the occurrence of severe PE is closely associated with the decline of trophoblast invasion and the failure of uterine spiral arteriole remodeling [10,11]. Failed spiral artery remodeling leads to reduced or abnormal uteroplacental perfusion, hypoxia, and damage to the syncytiotrophoblast, causing the release of factors such as SFlt-1, which induce endothelial cell dysfunction [12]. Moreover, uterine natural killer cells and macrophages are also involved in spiral artery remodeling, as are the extravillous trophoblasts (EVTs) [13]. It should be noted that EVTs fail to invade and remodel the spiral arteries in the first trimester of pregnancy [14]. In this study, therefore, we used placental trophoblasts to investigate PE.

Long noncoding RNAs (lncRNAs) are a class of single RNA molecules more than 200 nt in length, which do not encode for proteins but are involved in several regulatory processes, such as epigenetic regulation, transcription regulation, and posttranscriptional regulation [15,16]. MicroRNAs (miRNAs/miRs) are small, single-stranded RNA molecules with a length of 21–23 nt and are involved in cell differentiation, embryonic development, and disease occurrence and development [17–19]. lncRNAs can act as miRNA sponges, repressing miRNA expression and regulating mRNA expression at the posttranscriptional level. The analysis of mechanisms of miRNAs and lncRNAs action, and the use of the latest technology to investigate the association between miRNAs, lncRNAs, and diseases, has suggested that miRNAs and lncRNAs may be useful as novel biological markers for disease diagnosis and could provide new avenues for the treatment of diseases. Reports by Lv et al. suggested that the abnormal expression of placental lncRNAs and miRNAs may be associated with the occurrence and progression of PE [20–22]. In addition, increasing evidence suggests that miRNAs influence the behavior of placental trophoblasts by regulating the expression of their target genes, and participate in the progression of PE, playing an important role in its pathogenesis [23,24].

Previous studies have revealed that the migration capability of EVTs is regulated by several lncRNAs, such as maternally expressed 3 (lncRNA MEG3), colorectal neoplasia differentially expressed (lncRNA CRNDE), and growth arrest specific 5 (lncRNA-GAS5) [25–27]. The lncRNA WT1 antisense RNA (WT1-AS), an antisense transcript of Wilms tumor genes, regulates the invasiveness of multiple cells [28] and has been shown to be a vital regulator of cell proliferation, invasion, and migration [29–31]. Cui et al. suggested that WT1-AS suppressed cervical carcinoma cell proliferation, migration, and invasion through regulating the miR-330-5p/p53 axis [32]. However, the role of WT1-AS in the functioning of placental EVTs remains unknown. Wang et al. have reported that miR-186-5p is involved in various types of diseases, including ischemic stroke, atherosclerosis, diabetic cardiomyopathy, and cancer [33–36]. MiR-186-5p plays a role in disease development by regulating cell growth, invasion, migration, and apoptosis [33–36]. Previous studies have suggested that miR-186-5p is significantly increased in blood plasma during early-onset PE, and it plays a key role in the regulation of trophoblast cell viability [37,38]. The specific functions of miR-186-5p in PE and trophoblasts remain to be studied. Cell adhesion molecule 2 (CADM2), a member of the CADM family, has been found to maintain cell polarity, and previous studies have demonstrated that CADM2 could promote the migration and invasion of cancer cells, including those of endometrial cancer [39,40]. The role of CADM2 in EVT function remains to be explored. Thus, the miR-186-5p/CADM2 axis may interfere with PE through the regulation of the function of placental EVTs.

We hypothesized that lncRNA WT1-AS might affect trophoblast’s function in PE via regulating miR-186-5p/CADM2 axis. Hence, the purpose of this study was to investigate the effects of lncRNA WT1-AS on the function of HTR-8/Svneo cells and explore its possible involvement in the progression of PE, as well as to discover avenues for developing novel treatments for this condition.

2 Materials and methods

2.1 Cell culture

The human chorionic trophoblast line, HTR-8/Svneo, was obtained from American Type Culture Collection (ATCC, USA) and cultured in high-glucose Dulbecco’s modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum (FBS; Gibco, USA) with 5% CO2 at 37°C. Graham et al. developed the HTR-8/SVneo cell line (https://web.expasy.org/cellosaurus/CVCL_7162) [41]. A recent study showed that the cell line consists of two populations: trophoblast and stromal/mesenchymal cells [42]. 293T cells were obtained from ATCC (MA, USA) and cultured in DMEM supplemented with 10% FBS (Gibco, USA) with 5% CO2 at 37°C.

2.2 Dual-luciferase reporter assay [43]

The StarBase software (version 2.0; https://starbase.sysu.edu.cn/) was used to investigate the association between WT1-AS and miR-186a-5p, or miR-186a-5p and CADM2. To confirm the association between WT1-AS and miR-186a-5p, the 3′-untranslated region (UTR) of WT1-AS was obtained via PCR, including its target sequence. The 3′-UTR was fused with the pmirGLO vector (Promega, USA) to construct the WT1-AS wild-type (WT1-AS-WT) reporter vector and the WT1-AS mutant (WT1-AS-MUT) vector. A total of 293T cells (5 × 104 cells per well; American Type Culture Collection, USA) cultured for 24 h were co-transfected with WT1-AS-WT or WT1-AS-MUT luciferase reporter gene plasmids and miR-186a-5p mimic or mimic control for 48 h, using Lipofectamine® 2000 reagent (Invitrogen, USA), in accordance with the manufacturer’s protocol. After 24 h, the Dual-Luciferase Reporter Assay System (Promega, USA) was used to assess the luciferase activity.

2.3 Cell transfection

HTR-8/Svneo cells (5 × 104 cells per well) were cultured in six-well plates overnight and subsequently transfected with control plasmid, control-small interfering (si) RNA (Guangzhou Ribobio Co., Ltd., China), 100 nM inhibitor control (5′-GCCUCCGGCUUCGCACCUCU-3′; Shanghai GenePharma Co., Ltd., China), 100 nM mimic control (5′-UUCUCCGAACGUGUCACGUTT-3′; Shanghai GenePharma Co., Ltd.), WT1-AS plasmid, WT1-AS-siRNA (cat no. siG180524011008-1-5; Guangzhou Ribobio Co., Ltd.; https://www.ribobio.com/product_detail/?sku=siG180524011008-1-5), 100 nM miR-186-5p inhibitor (5′-AGCCCAAAAGGAGAAUUCUUUG-3′; Shanghai GenePharma Co., Ltd.), 100 nM miR-186-5p mimic (5′-CAAAGAAUUCUCCUUUUGGGCU-3′; Shanghai GenePharma Co., Ltd.), or CADM2 plasmid for 48 h, using Lipofectamine® 2000 reagent (Invitrogen, USA), according to the manufacturer’s protocol. Subsequently, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to evaluate efficiency of cell transfection.

2.4 qRT-PCR

The RNA content was isolated from cells using TRIzol® reagent (Life Technologies, USA) according to the manufacturer’s protocol. Then, the total RNA was reverse transcribed to cDNA using the PrimeScript RT Reagent Kit (TaKaRa, China). All reactions were conducted using the Prism 7000 Real-Time PCR system and SYBR qPCR Master Mix (Thermo Fisher Scientific, Inc., USA) according to the manufacturer’s protocol. Primer sequences were obtained from SANGON Biotech Co., Ltd., China. The following thermal cycling conditions were applied for qRT-PCR: initial denaturation for 5 min at 95°C, followed by 40 cycles of 10 s at 95°C and one cycle of 30 s at 60°C. GAPDH for mRNA and U6 for miRNA were used as the internal controls. The relative expression levels of WT1-AS, miR-186-5p, and CADM2 were analyzed using the 2−ΔΔCq method [44]. Primer sequences were synthesized by Sangon Biotech (Shanghai, China) and are listed in Table 1.

Table 1

Primer sequences for PCR

Gene name Sequences: 5′–3′
WT1-AS Forward, 5′-GCCTCTCTGTCCTCTTCTTTG-3′
Reverse, 5′-GCTGTGAGTCCTGGTGCTTA-3′
miR-186-5p Forward, 5′-TCAAAGAATTCTCCTTTTGGGCT-3′
Reverse, 5′-CGCTTCACGAATTTGCGTGTCAT-3′
CADM2 Forward, 5′-TCTATTCCAACAAGTCAGAAAATAATG-3′
Reverse, 5′-CGCTTAGACTTGATTTTGACGG-3′
GAPDH Forward, 5′-ATCACTGCCACCCAGAAGAC-3′
Reverse, 5′-TTTCTAGACGGCAGGTCAGG-3′
U6 Forward, 5′-CTCGCTTCGGCAGCACA-3′
Reverse, 5′-AACGCTTCACGAATTTGCGT-3′

2.5 MTT assay [45]

Transfected cells (104 cells/well) were seeded in a 96-well plate overnight. Subsequently, 10 μL 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) solution was added to each well, followed by incubation for 4 h. The purple formazan crystals were dissolved in 100 μL DMSO (Sigma-Aldrich, USA), and cell proliferation was subsequently measured at optical density (OD)570 for 10 min, using a microplate reader (Jupiter G19060; Dorval, Canada).

2.6 Transwell assay [46]

Transwell assays were conducted using Matrigel-free chambers (pore size, 8 μm; Costar; Corning Inc., USA) and Matrigel chambers, to study cell migration and invasion, respectively. Cells (2 × 104) were plated into the upper chambers (Thermo Fisher Scientific, Inc., USA) and maintained in serum-free DMEM medium after transfection for 48 h. DMEM containing 10% FBS was added into the lower chambers. After 24 h, the migratory or invasive cells in the lower chambers were treated with 4% paraformaldehyde (Sigma) and 0.1% crystal violet (Beyotime Institute of Biotechnology, China) for 20 min and counted under a light microscope (magnification: ×100; Olympus Corporation) in five randomly selected fields.

2.7 Flow cytometry (FCM) analysis [47]

FCM analysis was performed to detect cell apoptosis using the Annexin V-FITC/PI apoptosis detection kit (Beyotime Institute of Biotechnology, China). Transfected cells were collected following trypsinization and resuspended in Annexin V-FITC Binding Solution. The cell suspension (100 µL) was cultured with 5 µL annexin V-FITC and PI (BD Biosciences, USA) according to the manufacturer’s protocol. Stained cells were counted using a FACSCalibur flow cytometer (BD Biosciences, USA) and Kaluza Analysis (version 2.1.1.20653; Beckman Coulter, Inc., USA).

2.8 Western blotting [48]

Transfected cells were separated using radioimmunoprecipitation assay buffer (Beyotime Institute of Biotechnology, China) and subsequently centrifuged at 4°C for 15 min to collect the total protein content. Proteins were quantified using the BCA Protein Assay Kit (Beyotime Institute of Biotechnology, China) and loaded in 10% sodium dodecyl-sulfate polyacrylamide gel electrophoresis gel. The separated samples were transferred onto polyvinylidene fluoride membranes and incubated with 5% skim milk in PBS-Tween 20 (PBST) solution for 1 h. The membranes were incubated with primary antibodies against CADM2 (cat. no. ab64873; 1:2,000; Abcam, UK), and GAPDH (cat. no. 5174; 1:1,000; Abcam, UK) overnight at 4°C. Subsequently, the membranes were washed with PBST and incubated with secondary antibodies (cat no. ab7090; 1:2,000; Abcam, UK). Finally, protein bands were quantified using an enhanced chemiluminescence substrate (Cytiva, USA).

2.9 Statistical analysis

SPSS software (version 20.0; IBM Corp., USA) was used for statistical analyses. Data are presented as the mean ± SD from three independent experiments. We used the D method of the normality test (Kolmogorov–Smirnov test) to test the normality of the data in SPSS. Differences among multiple groups were estimated using one-way analysis of variance (ANOVA) and Student’s t-test. *P < 0.05 and **P < 0.01 indicated statistically significant differences.

3 Results

3.1 WT1-AS plasmid affects the viability, migration, and invasion of HTR-8/SVneo cells

To explore the role of WT1-AS in HTR-8/SVneo cells, control plasmid and WT1-AS plasmid were transfected into HTR-8/SVneo cells for 48 h. The results indicate that WT1-AS plasmid significantly increased WT1-AS expression (Figure 1a) and inhibited viability (Figure 1b), migration (Figure 1c and d), and invasion (Figure 1e and f) in HTR-8/SVneo cells, compared to that in the control group.

Figure 1 Effects of WT1-AS-plasmid on HTR-8/SVneo cell viability, migration, and invasion. (a) qRT-PCR analysis was used to determine the transfection efficiency of control plasmid and WT1-AS plasmid in HTR-8/SVneo cells. (b) The viability of HTR-8/SVneo cells was determined using the MTT assay. HTR-8/SVneo cell migration (c) and invasion (e) (magnification: ×100; bar = 100 μm) were assessed by Transwell assay. The number of migratory cells (d) and invasive cells (f) were determined. ** P < 0.01 vs control plasmid. WT1-AS, WT1 antisense RNA.
Figure 1

Effects of WT1-AS-plasmid on HTR-8/SVneo cell viability, migration, and invasion. (a) qRT-PCR analysis was used to determine the transfection efficiency of control plasmid and WT1-AS plasmid in HTR-8/SVneo cells. (b) The viability of HTR-8/SVneo cells was determined using the MTT assay. HTR-8/SVneo cell migration (c) and invasion (e) (magnification: ×100; bar = 100 μm) were assessed by Transwell assay. The number of migratory cells (d) and invasive cells (f) were determined. ** P < 0.01 vs control plasmid. WT1-AS, WT1 antisense RNA.

3.2 WT1-AS plasmid affects apoptosis of HTR-8/SVneo cells

FCM assay was performed to explore the effect of WT1-AS in HTR-8/SVneo cells apoptosis. FCM assay demonstrated that transfection with WT1-AS plasmid significantly promoted apoptosis of HTR-8/SVneo cells (Figure 2a and b).

Figure 2 Effects of WT1-AS plasmid on apoptosis of HTR-8/SVneo cells. (a and b) Flow cytometry analysis of apoptotic HTR-8/SVneo cells. ** P < 0.01 vs control plasmid. WT1-AS, WT1 antisense RNA.
Figure 2

Effects of WT1-AS plasmid on apoptosis of HTR-8/SVneo cells. (a and b) Flow cytometry analysis of apoptotic HTR-8/SVneo cells. ** P < 0.01 vs control plasmid. WT1-AS, WT1 antisense RNA.

3.3 MiR-186a-5p directly targets WT1-AS

To analyze the mechanism of the role of WT1-AS in HTR-8/SVneo cells, the target relationship between WT1-AS and miR-186-5p was determined. StarBase analysis revealed a binding site between WT1-AS and miR-186-5p (Figure 3a), and this association was confirmed via the dual-luciferase reporter assay (Figure 3b). Compared with cells co-transfected with WT1-AS-WT and mimic control, the luciferase activity of cells co-transfected with WT1-AS-WT and miR-186-5p mimic significantly reduced (Figure 3b). While there were no significant differences in the luciferase activity of cells co-transfected with WT1-AS-WT and mimic control, and the cells co-transfected with WT1-AS-WT and miR-186-5p mimic were found.

Figure 3 miR-186-5p directly targets lncRNA WT1-AS. (a) A schematic of miR-186a-5p binding site in lncRNA WT1-AS 3′-UTR. (b) The interaction between miR-186a-5p and lncRNA WT1-AS was confirmed via dual-luciferase reporter assay. ** P < 0.01 vs mimic control. miR, microRNA; lncRNA, long noncoding RNA; WT1-AS, WT1 antisense RNA; WT, wild-type; MUT, mutant; UTR, untranslated region.
Figure 3

miR-186-5p directly targets lncRNA WT1-AS. (a) A schematic of miR-186a-5p binding site in lncRNA WT1-AS 3′-UTR. (b) The interaction between miR-186a-5p and lncRNA WT1-AS was confirmed via dual-luciferase reporter assay. ** P < 0.01 vs mimic control. miR, microRNA; lncRNA, long noncoding RNA; WT1-AS, WT1 antisense RNA; WT, wild-type; MUT, mutant; UTR, untranslated region.

3.4 WT1-AS negatively regulates miR-186a-5p expression in HTR-8/SVneo cells

We then explored whether WT1-AS could regulate miR-186a-5p expression in HTR-8/SVneo cells. qRT-PCR analysis indicated that transfection with WT1-AS-siRNA significantly decreased WT1-AS expression in HTR-8/SVneo cells, compared to that in the control siRNA group (Figure 4a). Furthermore, downregulation of miR-186-5p notably decreased miR-186-5p levels in HTR-8/SVneo cells (Figure 4b). Moreover, transfection with WT1-AS-siRNA markedly increased miR-186-5p levels in HTR-8/SVneo cells, which was reversed after co-transfection with miR-186-5p inhibitor (Figure 4c).

Figure 4 WT1-AS knockdown upregulates miR-186a-5p expression in HTR-8/SVneo cells. (a) qRT-PCR analysis of WT1-AS in HTR-8/SVneo cells transfected with control siRNA or WT1-AS siRNA. (b) Determination of miR-186-5p levels in HTR-8/SVneo cells transfected with inhibitor control or miR-186-5p inhibitor. (c) mRNA expression of miR-186-5p in HTR-8/SVneo cells transfected with control siRNA, WT1-AS-siRNA, WT1-AS-siRNA + inhibitor control, or WT1-AS-siRNA + miR-186-5p inhibitor was determined using qRT-PCR. ** P < 0.01 vs control siRNA; ## P < 0.01 vs inhibitor control; && P < 0.01 vs WT1-AS-siRNA + inhibitor control. WT1-AS, WT1 antisense RNA; miR, microRNA; RT-qPCR, reverse transcription-quantitative PCR; si, small interfering.
Figure 4

WT1-AS knockdown upregulates miR-186a-5p expression in HTR-8/SVneo cells. (a) qRT-PCR analysis of WT1-AS in HTR-8/SVneo cells transfected with control siRNA or WT1-AS siRNA. (b) Determination of miR-186-5p levels in HTR-8/SVneo cells transfected with inhibitor control or miR-186-5p inhibitor. (c) mRNA expression of miR-186-5p in HTR-8/SVneo cells transfected with control siRNA, WT1-AS-siRNA, WT1-AS-siRNA + inhibitor control, or WT1-AS-siRNA + miR-186-5p inhibitor was determined using qRT-PCR. ** P < 0.01 vs control siRNA; ## P < 0.01 vs inhibitor control; && P < 0.01 vs WT1-AS-siRNA + inhibitor control. WT1-AS, WT1 antisense RNA; miR, microRNA; RT-qPCR, reverse transcription-quantitative PCR; si, small interfering.

3.5 WT1-AS-siRNA affects the function of HTR-8/SVneo cells by regulating miR-186-5p

The results from MTT and transwell assays shown in Figure 5 suggest that WT1-AS-siRNA significantly promoted HTR-8/SVneo cell viability (Figure 5a), migration (Figure 5b and c), and invasion (Figure 5d and e), compared to that of control siRNA. Notably, transfection with WT1-AS-siRNA suppressed apoptosis in HTR-8/SVneo cells (Figure 5f and g), which was reversed after miR-186-5p inhibitor transfection.

Figure 5 Effects of WT1-AS-siRNA on the function of HTR-8/SVneo cells. (a) Viability of HTR-8/SVneo cells was checked by the MTT assay. HTR-8/SVneo cell migration (b) and invasion (d) (magnification: ×100; bar = 100 μm) were evaluated using Transwell assay. The number of migratory cells (c) and invasive cells (e) were determined. (f and g) Flow cytometry was applied to assess apoptosis of HTR-8/SVneo cells. One-way ANOVA followed by Tukey’s post hoc test was used for data analysis. ** P < 0.01 vs control-siRNA; ## P < 0.01 vs WT1-AS-siRNA + inhibitor control. WT1-AS, WT1 antisense RNA; si, small interfering.
Figure 5

Effects of WT1-AS-siRNA on the function of HTR-8/SVneo cells. (a) Viability of HTR-8/SVneo cells was checked by the MTT assay. HTR-8/SVneo cell migration (b) and invasion (d) (magnification: ×100; bar = 100 μm) were evaluated using Transwell assay. The number of migratory cells (c) and invasive cells (e) were determined. (f and g) Flow cytometry was applied to assess apoptosis of HTR-8/SVneo cells. One-way ANOVA followed by Tukey’s post hoc test was used for data analysis. ** P < 0.01 vs control-siRNA; ## P < 0.01 vs WT1-AS-siRNA + inhibitor control. WT1-AS, WT1 antisense RNA; si, small interfering.

3.6 CADM2 is a direct target of miR-186a-5p

To confirm the underlying mechanism of miR-186a-5p in HTR-8/SVneo cells, the potential targets of imiR-186a-5p were investigated using TargetScan. TargetScan analysis revealed a binding site between CADM2 and miR-186a-5p (Figure 6a), and this association was confirmed via the dual-luciferase reporter assay (Figure 6b).

Figure 6 Correlation between miR-186-5p and CADM2. (a) StarBase analysis predicted the relationship between miR-186a-5p and CADM2. (b) The association between miR-186-5p and CADM2 was verified via the dual-luciferase reporter assay. ** P < 0.01 vs mimic control. miR, microRNA; CADM2, cell adhesion molecule 2.
Figure 6

Correlation between miR-186-5p and CADM2. (a) StarBase analysis predicted the relationship between miR-186a-5p and CADM2. (b) The association between miR-186-5p and CADM2 was verified via the dual-luciferase reporter assay. ** P < 0.01 vs mimic control. miR, microRNA; CADM2, cell adhesion molecule 2.

3.7 MiR-186a-5p negatively regulates CADM2 expression in HTR-8/SVneo cells

To confirm the regulatory effect of miR-186a-5p on HTR-8/SVneo cells, mimic control, miR-186a-5p mimic, control plasmid, CADM2 plasmid, miR-186a-5p mimic + control plasmid, and miR-186a-5p mimic + CADM2 plasmid were transfected into HTR-8/SVneo cells. qRT-PCR results indicated that transfection with miR-186-5p mimic and CADM2 plasmid significantly increased miR-186-5p and CADM2 levels in HTR-8/SVneo cells, respectively (Figure 7a and b). Notably, miR-186-5p mimic decreased CADM2 protein and mRNA expression levels in HTR-8/SVneo cells, which was reversed after co-transfection with CADM2 plasmid (Figure 7c and d).

Figure 7 miR-186-5p negatively regulates CADM2 expression in HTR-8/SVneo cells. (a) qRT-PCR analysis of miR-186-5p in HTR-8/SVneo cells transfected with mimic control or miR-186-5p mimic. (b) qRT-PCR analysis was performed to detect CADM2 expression in HTR-8/SVneo cells transfected by control plasmid or CADM2 plasmid. (c and d) Determination of CADM2 expression levels in HTR-8/SVneo cells transfected by mimic control, miR-186-5p mimic, miR-186-5p mimic + control plasmid, or miR-186-5p mimic + CADM2 plasmid using western blot and qRT-PCR analyses. ** P < 0.01 vs mimic control; ## P < 0.01 vs control-plasmid; && P < 0.01 vs miR-186-5p mimic + control-plasmid. miR, microRNA; CADM2, cell adhesion molecule 2; RT-qPCR, reverse transcription-quantitative PCR.
Figure 7

miR-186-5p negatively regulates CADM2 expression in HTR-8/SVneo cells. (a) qRT-PCR analysis of miR-186-5p in HTR-8/SVneo cells transfected with mimic control or miR-186-5p mimic. (b) qRT-PCR analysis was performed to detect CADM2 expression in HTR-8/SVneo cells transfected by control plasmid or CADM2 plasmid. (c and d) Determination of CADM2 expression levels in HTR-8/SVneo cells transfected by mimic control, miR-186-5p mimic, miR-186-5p mimic + control plasmid, or miR-186-5p mimic + CADM2 plasmid using western blot and qRT-PCR analyses. ** P < 0.01 vs mimic control; ## P < 0.01 vs control-plasmid; && P < 0.01 vs miR-186-5p mimic + control-plasmid. miR, microRNA; CADM2, cell adhesion molecule 2; RT-qPCR, reverse transcription-quantitative PCR.

3.8 MiR-186-5p mimic affects the function of HTR-8/SVneo cells by regulating CADM2

Finally, we studied whether miR-186-5p mimic affects the function of HTR-8/SVneo cells by targeting CADM2. Transfection with the miR-186-5p mimic dramatically increased HTR-8/SVneo cell viability (Figure 8a) and enhanced the migratory (Figure 8b and c) and invasive (Figure 8d and e) abilities of cells, compared to that in the mimic control group. The FCM analysis indicated a notable decrease in apoptosis following transfection with the miR-186-5p mimic, compared to that of the mimic control group (Figure 8f and g).

Figure 8 Effects of miR-186-5p mimic on the functions of HTR-8/SVneo cells. (a) Viability of HTR-8/SVneo cells was assessed using MTT assay. Transwell assay was used to analyze HTR-8/SVneo cell migration (b) and invasion (d) (magnification: ×100; bar = 100 μm). The number of migratory cells (c) and invasive cells (e) was determined. (f) Flow cytometry analysis of apoptosis in HTR-8/SVneo cells. (g) Quantification of apoptotic cells. ** P < 0.01 vs mimic control; ## P < 0.01 vs miR-186-5p mimic + control-plasmid. miR, microRNA.
Figure 8

Effects of miR-186-5p mimic on the functions of HTR-8/SVneo cells. (a) Viability of HTR-8/SVneo cells was assessed using MTT assay. Transwell assay was used to analyze HTR-8/SVneo cell migration (b) and invasion (d) (magnification: ×100; bar = 100 μm). The number of migratory cells (c) and invasive cells (e) was determined. (f) Flow cytometry analysis of apoptosis in HTR-8/SVneo cells. (g) Quantification of apoptotic cells. ** P < 0.01 vs mimic control; ## P < 0.01 vs miR-186-5p mimic + control-plasmid. miR, microRNA.

3.9 WT1-AS-siRNA-reduced CADM2 expression in HTR-8/SVneo cells

Finally, to explore the effect of WT1-AS-siRNA on CADM2 expression in HTR-8/SVneo cells, HTR-8/SVneo cells were transfected with control-siRNA, WT1-AS-siRNA, WT1-AS siRNA + inhibitor control, or WT1-AS siRNA + miR-186-5p inhibitor. The results indicated that compared with the control siRNA group, WT1-AS siRNA significantly reduced CADM2 protein and mRNA expression in HTR-8/SVneo cells, and this reduction was reversed by miR-186-5p inhibitor (Figure 9a and b).

Figure 9 WT1-AS-siRNA-reduced CADM2 expression in HTR-8/SVneo cells. HTR-8/SVneo cells were transfected with control siRNA, WT1-AS siRNA, WT1-AS siRNA + inhibitor control, or WT1-AS siRNA + miR-186-5p inhibitor. (a) Protein expression of CADM2 in HTR-8/SVneo cells was determined using western blotting. (b) mRNA expression of CADM2 in HTR-8/SVneo cells was determined using RT-qPCR. ** P < 0.01 vs control siRNA; ## P < 0.01 vs WT1-AS siRNA + inhibitor control. WT1-AS, WT1 antisense RNA; si, small interfering; miR, microRNA; RT-qPCR, reverse transcription-quantitative PCR.
Figure 9

WT1-AS-siRNA-reduced CADM2 expression in HTR-8/SVneo cells. HTR-8/SVneo cells were transfected with control siRNA, WT1-AS siRNA, WT1-AS siRNA + inhibitor control, or WT1-AS siRNA + miR-186-5p inhibitor. (a) Protein expression of CADM2 in HTR-8/SVneo cells was determined using western blotting. (b) mRNA expression of CADM2 in HTR-8/SVneo cells was determined using RT-qPCR. ** P < 0.01 vs control siRNA; ## P < 0.01 vs WT1-AS siRNA + inhibitor control. WT1-AS, WT1 antisense RNA; si, small interfering; miR, microRNA; RT-qPCR, reverse transcription-quantitative PCR.

4 Discussion

PE is a hypertensive condition affecting pregnant women. Its clinical manifestations vary; however, hypertension and proteinuria are common symptoms [49]. PE and placental insufficiency are closely related. The placenta is essential for the fetal development as fetal blood and maternal blood exchange nutrients through it. The placenta has two main functions, endocrine signaling and invasion, and these functions depend on the EVTs [50]. The main reason behind the onset of PE is the failure of remodeling of the uterine spiral artery caused by insufficient EVT infiltration.

HTR-8/SVneo cells, developed by Graham et al. [41], have been widely used to study PE in vitro [51–53]. Thus, this study used HTR-8/SVneo cells to study PE in vitro. In recent years, more and more studies have shown that lncRNA plays a key role in PE [20,25–27]. lncRNA NEAT1 silencing improves Treg/Th17 imbalance in PE via the miR-485-5p/AIM2 axis [21]. lncRNA MEG3 has been reported to inhibit trophoblast invasion [26]. It has been confirmed that lncRNA CRNDE could regulate trophoblast cell proliferation, invasion, and migration through modulating miR-1277 [26]. In this study, we used HTR-8/SVneo cells to explore the role of WT1-AS in the function of placental EVTs. First, through database analysis, we found that WT1-AS is expressed in the placenta (https://www.ncbi.nlm.nih.gov/gene/51352). In addition, we first confirmed that lncRNA WT1-AS, miR-186-5p, and CADM2 were stably expressed in HTR-8/SVneo cells (Figures 4 and 7) and then proceeded with subsequent experiments. We observed that lncRNA WT1-AS inhibited various functions of HTR-8/SVneo cells, including cell growth, migration, and invasion, and promoted apoptosis.

Accumulating evidence suggests that lncRNAs can act as miRNA sponges, repressing miRNA expression and regulating mRNA expression at the posttranscriptional level [24,54]. To further determine the molecular mechanism of WT1-AS in placental EVTs, the binding sites between WT1-AS and miR-186-5p were predicted and verified. The results indicated a negative correlation between miR-186-5p and WT1-AS levels in HTR-8/SVneo cells. MiR-186-5p has also been shown to be involved in PE [37,38]. Gusar et al. revealed that miR-186-5p is upregulated in blood plasma during early onset PE [37]. Hsa_circ_0001326 suppressed human trophoblast SWAN71 viability by regulating the miR-186-5p/p27 kip1 axis [38]. In this study, WT1-AS knockdown promoted the function of placental EVTs by upregulating miR-186-5p expression. The present study also verified the relationship between miR-186-5p and CADM2. CADM2, a protein-coding gene, acts as a tumor suppressor in cancer through inhibiting cell migration and invasion [39,40]. He et al. reported that CADM2 could inhibit human renal clear cell carcinoma by promoting DNA promoter methylation and/or loss of heterozygosity [55]. To determine whether miR-186-5p regulates the proliferation, migration, and invasion of placental EVTs by regulating CADM2, miR-186-5p and CADM2 were upregulated in HTR-8/SVneo cells. The results indicated that CADM2 negatively regulates miR-186-5p expression. In addition, miR-186-5p promoted the function of HTR-8/SVneo cells after the downregulation of CADM2 expression. In this study, the mechanism by which CADM2 affected the function of HTR-8/SVneo cells still needs to be further explored.

The current study had some limitations. For example, EVTs fail to invade and remodel the spiral arteries in the first trimester of pregnancy [14], and HTR-8/SVneo cell is a model of first-trimester EVT [41]. Thus, our study models process that take place in the first trimester (EVT-mediated remodeling of the spiral arteries), but PE is not evident until the mid-second trimester. But in fact, miRNA biomarkers for PE can be detected in maternal circulation as early as the first trimester, although PE is not evident until later in pregnancy [56–58]. Besides, this work was performed using HTR-8/SVneo cells and needs validation using primary human first trimester EVTs. Whether the change of WT1-AS/miR-186a-5p/CADM2 axis affect cell cycle in trophoblasts was not investigated. We also did not perform migration and invasion assays on HTR-8/SVneo cells with cell cycle arrest to explain the effects of proliferation. Altered angiogenic factors are known contributors to the pathogenesis of PE, and this study did not analyze the effect of WT1-AS on angiogenic factor receptors. In addition, there is a significant difference between the conditions of the in vitro experiments and those of PE. Moreover, the role of lncRNA WT1-AS/miR-186-5p/CADM2 axis in the function of other placental EVTs (such as primary human first trimester EVTs and other trophoblast cell-lines such as JEG-3, BeWo cells or JAR cells) needs to be explored, as does the role of lncRNA WT1-AS/miR-186-5p/CADM2 axis in PE animal models. The expression of lncRNA WT1-AS in PE and non-PE patients should be investigated. Moreover, roles of lncRNA WT1-AS/miR-186-5p/CADM2 in PE patients, and the relationship between their expression and the clinicopathological parameters of PE patients, also need to be determined. We will address these issues in the future.

5 Conclusion

Our findings suggest that lncRNA WT1-AS regulates HTR-8/SVneo cell proliferation and invasion through the miR-186-5p/CADM2 axis, and participates in PE, indicating that targeting the miR-186-5p/CADM2 axis can provide novel opportunities for patients with PE.

Acknowledgments

Not applicable.

  1. Funding information: No funding was received.

  2. Author contributions: Qun Qiu: study design, data collection, statistical analysis, data interpretation, and manuscript preparation. Juan Tan: data collection, statistical analysis, and manuscript preparation. All authors read and approved the final manuscript.

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

  4. Data availability statement: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

References

[1] Rambaldi MP, Weiner E, Mecacci F, Bar J, Petraglia F. Immunomodulation and preeclampsia. Best Pract Res Clin Obstet Gynaecol. 2019;60:87–96.10.1016/j.bpobgyn.2019.06.005Search in Google Scholar PubMed

[2] Beckers KF, Sones JL. Maternal microbiome and the hypertensive disorder of pregnancy, preeclampsia. Am J Physiol Heart Circ Physiol. 2020;318:H1–H10.10.1152/ajpheart.00469.2019Search in Google Scholar PubMed

[3] Orlovic Vlaho M, Tomic V, Vukojevic K, Vasilj A, Pejic R, Lesko J, et al. CD25(+) FOXP3(+) and CD4(+) CD25(+) cells distribution in decidual departments of women with severe and mild pre-eclampsia: Comparison with healthy pregnancies. Am J Reprod Immunol. 2020;84:e13281.10.1111/aji.13281Search in Google Scholar PubMed

[4] Jena MK, Sharma NR, Petitt M, Maulik D, Nayak NR. Pathogenesis of preeclampsia and therapeutic approaches targeting the placenta. Biomolecules. 2020;10:953.10.3390/biom10060953Search in Google Scholar PubMed PubMed Central

[5] Jaatinen N, Jääskeläinen T, FINNPEC, Laivuori H, Ekholm E. The non-traditional and familial risk factors for preeclampsia in the FINNPEC cohort. Pregnancy Hypertens. 2021;23:48–55.10.1016/j.preghy.2020.11.001Search in Google Scholar PubMed

[6] Taysi S, Tascan AS, Ugur MG, Demir M. Radicals, oxidative/nitrosative stress and preeclampsia. Mini Rev Med Chem. 2019;19:178–93.10.2174/1389557518666181015151350Search in Google Scholar PubMed

[7] Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: pathophysiology, challenges, and perspectives. Circ Res. 2019;124:1094–112.10.1161/CIRCRESAHA.118.313276Search in Google Scholar PubMed

[8] Dymara-Konopka W, Laskowska M, Oleszczuk J. Preeclampsia - current management and future approach. Curr Pharm Biotechnol. 2018;19:786–96.10.2174/1389201019666180925120109Search in Google Scholar PubMed

[9] Abbas Y, Turco MY, Burton GJ, Moffett A. Investigation of human trophoblast invasion in vitro. Hum Reprod Update. 2020;26:501–13.10.1093/humupd/dmaa017Search in Google Scholar PubMed PubMed Central

[10] Burton GJ, Redman CW, Roberts JM, Moffett A. Pre-eclampsia: pathophysiology and clinical implications. BMJ. 2019;366:l2381.10.1136/bmj.l2381Search in Google Scholar PubMed

[11] Saito S, Nakashima A. A review of the mechanism for poor placentation in early-onset preeclampsia: the role of autophagy in trophoblast invasion and vascular remodeling. J Reprod Immunol. 2014;101–102:80–8.10.1016/j.jri.2013.06.002Search in Google Scholar PubMed

[12] Ahmed A, Rezai H, Broadway-Stringer S. Evidence-based revised view of the pathophysiology of preeclampsia. Adv Exp Med Biol. 2017;956:355–74.10.1007/5584_2016_168Search in Google Scholar PubMed

[13] Faas MM, de Vos P. Uterine NK cells and macrophages in pregnancy. Placenta. 2017;56:44–52.10.1016/j.placenta.2017.03.001Search in Google Scholar PubMed

[14] Wallace AE, Fraser R, Cartwright JE. Extravillous trophoblast and decidual natural killer cells: a remodelling partnership. Hum Reprod Update. 2012;18:458–71.10.1093/humupd/dms015Search in Google Scholar PubMed PubMed Central

[15] Zhao Z, Sun W, Guo Z, Zhang J, Yu H, Liu B. Mechanisms of lncRNA/microRNA interactions in angiogenesis. Life Sci. 2020;254:116900.10.1016/j.lfs.2019.116900Search in Google Scholar PubMed

[16] Qian X, Zhao J, Yeung PY, Zhang QC, Kwok CK. Revealing lncRNA structures and interactions by sequencing-based approaches. Trends Biochem Sci. 2019;44:33–52.10.1016/j.tibs.2018.09.012Search in Google Scholar PubMed

[17] Wang JY, Yang Y, Ma Y, Wang F, Xue A, Zhu J, et al. Potential regulatory role of lncRNA-miRNA-mRNA axis in osteosarcoma. Biomed Pharmacother. 2020;121:109627.10.1016/j.biopha.2019.109627Search in Google Scholar PubMed

[18] Yang Y, Yujiao W, Fang W, Linhui Y, Ziqi G, Zhichen W, et al. The roles of miRNA, lncRNA and circRNA in the development of osteoporosis. Biol Res. 2020;53:40.10.1186/s40659-020-00309-zSearch in Google Scholar PubMed PubMed Central

[19] Tiwari A, Mukherjee B, Dixit M. MicroRNA Key to Angiogenesis Regulation: MiRNA Biology and Therapy. Curr Cancer Drug Targets. 2018;18266–77.10.2174/1568009617666170630142725Search in Google Scholar PubMed

[20] Chen JY, Zhang YG, Tan WQ, Gao HC, Xiao SX, Gao JH, et al. Silencing of long non-coding RNA NEAT1 improves Treg/Th17 imbalance in preeclampsia via the miR-485-5p/AIM2 axis. Bioengineered. 2021;12:8768–77.10.1080/21655979.2021.1982306Search in Google Scholar PubMed PubMed Central

[21] Lv Y, Lu C, Ji X, Miao Z, Long W, Ding H, et al. Roles of microRNAs in preeclampsia. J Cell Physiol. 2019;234:1052–61.10.1002/jcp.27291Search in Google Scholar PubMed

[22] Skalis G, Katsi V, Miliou A, Georgiopoulos G, Papazachou O, Vamvakou G, et al. MicroRNAs in preeclampsia. Microrna. 2019;8:28–35.10.2174/2211536607666180813123303Search in Google Scholar PubMed

[23] Kamrani A, Alipourfard I, Ahmadi-Khiavi H, Yousefi M, Rostamzadeh D, Izadi M, et al. The role of epigenetic changes in preeclampsia. Biofactors. 2019;45:712–24.10.1002/biof.1542Search in Google Scholar PubMed

[24] Liu S, Xie X, Lei H, Zou B, Xie L. Identification of Key circRNAs/lncRNAs/miRNAs/mRNAs and pathways in preeclampsia using bioinformatics analysis. Med Sci Monit. 2019;25:1679–93.10.12659/MSM.912801Search in Google Scholar PubMed PubMed Central

[25] Tao H, Liu X, Liu X, Liu W, Wu D, Wang R, et al. LncRNA MEG3 inhibits trophoblast invasion and trophoblast-mediated VSMC loss in uterine spiral artery remodeling. Mol Reprod Dev. 2019;86:686–95.10.1002/mrd.23147Search in Google Scholar PubMed

[26] Zhu H, Kong L. LncRNA CRNDE regulates trophoblast cell proliferation, invasion, and migration via modulating miR-1277. Am J Transl Res. 2019;11:5905–18.Search in Google Scholar

[27] Wang MM, Zhong JX, Xiang YY. LncRNA-GAS5 related to the processes of recurrent pregnancy loss by regulating Th1/Th2 balance. Kaohsiung J Med Sci. 2021;37:479–86.10.1002/kjm2.12360Search in Google Scholar PubMed

[28] Wang J, Xi C, Yang X, Lu X, Yu K, Zhang Y, et al. LncRNA WT1-as inhibits triple-negative breast cancer cell migration and invasion by downregulating transforming growth factor beta1. Cancer Biother Radiopharm. 2019;34:671–5.10.1089/cbr.2019.2925Search in Google Scholar

[29] Wu C, Yang J, Li R, Lin X, Wu J, Wu J. LncRNA WT1-AS/miR-494-3p regulates cell proliferation, apoptosis, migration and invasion via PTEN/PI3K/AKT signaling pathway in non-small cell lung cancer. Onco Targets Ther. 2021 Feb 9;14:891–904.10.2147/OTT.S278233Search in Google Scholar PubMed PubMed Central

[30] Du T, Zhang B, Zhang S, Jiang X, Zheng P, Li J, et al. Decreased expression of long non-coding RNA WT1-AS promotes cell proliferation and invasion in gastric cancer. Biochim Biophys Acta. 2016;1862:12–9.10.1016/j.bbadis.2015.10.001Search in Google Scholar PubMed

[31] Wang Q, Ge X, Zhang J, Chen L. Effect of lncRNA WT1-AS regulating WT1 on oxidative stress injury and apoptosis of neurons in Alzheimer’s disease via inhibition of the miR-375/SIX4 axis. Aging (Albany NY). 2020;12:23974–95.10.18632/aging.104079Search in Google Scholar PubMed PubMed Central

[32] Cui L, Nai M, Zhang K, Li L, Li R. lncRNA WT1-AS inhibits the aggressiveness of cervical cancer cell via regulating p53 expression via sponging miR-330-5p. Cancer Manag Res. 2019;11:651–67.10.2147/CMAR.S176525Search in Google Scholar PubMed PubMed Central

[33] Wang R, Bao H, Zhang S, Li R, Chen L, Zhu Y. miR-186-5p promotes apoptosis by targeting IGF-1 in SH-SY5Y OGD/R model. Int J Biol Sci. 2018;14:1791–9.10.7150/ijbs.25352Search in Google Scholar PubMed PubMed Central

[34] Zhang S, Zhu X, Li G. E2F1/SNHG7/miR-186-5p/MMP2 axis modulates the proliferation and migration of vascular endothelial cell in atherosclerosis. Life Sci. 2020;257:118013.10.1016/j.lfs.2020.118013Search in Google Scholar PubMed

[35] Liu Y, Zheng W, Pan Y, Hu J. Low expression of miR-186-5p regulates cell apoptosis by targeting toll-like receptor 3 in high glucose-induced cardiomyocytes. J Cell Biochem. 2019;120:9532–8.10.1002/jcb.28229Search in Google Scholar PubMed

[36] Feng H, Zhang Z, Qing X, French SW, Liu D. miR-186-5p promotes cell growth, migration and invasion of lung adenocarcinoma by targeting PTEN. Exp Mol Pathol. 2019;108:105–13.10.1016/j.yexmp.2019.04.007Search in Google Scholar PubMed

[37] Gusar V, Timofeeva A, Chagovets V, Kan N, Vasilchenko O, Prozorovskaya K, et al. Preeclampsia: The interplay between oxygen-sensitive miRNAs and erythropoietin. J Clin Med. 2020;9:574.10.3390/jcm9020574Search in Google Scholar PubMed PubMed Central

[38] Tan J, Zhong Z, Xu W, Zhang N. Overexpressed Hsa_circ_0001326 contributes to the decreased cell viability in SWAN71 cells by regulating MiR-186-5p/p27 Kip1 axis. Biol Pharm Bull. 2021;44:507–14.10.1248/bpb.b20-00755Search in Google Scholar PubMed

[39] Liu N, Yang C, Bai W, Wang Z, Wang X, Johnson M, et al. CADM2 inhibits human glioma proliferation, migration and invasion. Oncol Rep. 2019;41:2273–80.10.3892/or.2019.7010Search in Google Scholar PubMed

[40] He Z, Xu H, Meng Y, Kuang Y. miR-944 acts as a prognostic marker and promotes the tumor progression in endometrial cancer. Biomed Pharmacother. 2017;88:902–10.10.1016/j.biopha.2017.01.117Search in Google Scholar PubMed

[41] Graham CH, Hawley TS, Hawley RG, MacDougall JR, Kerbel RS, Khoo N, et al. Establishment and characterization of first trimester human trophoblast cells with extended lifespan. Exp Cell Res. 1993;206:204–11.10.1006/excr.1993.1139Search in Google Scholar PubMed

[42] Abou-Kheir W, Barrak J, Hadadeh O, Daoud G. HTR-8/SVneo cell line contains a mixed population of cells. Placenta. 2017;50:1–7.10.1016/j.placenta.2016.12.007Search in Google Scholar PubMed

[43] Clément T, Salone V, Rederstorff M. Dual luciferase gene reporter assays to study miRNA function. Methods Mol Biol. 2015;1296:187–98.10.1007/978-1-4939-2547-6_17Search in Google Scholar PubMed

[44] Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–8.10.1006/meth.2001.1262Search in Google Scholar PubMed

[45] Kumar P, Nagarajan A, Uchil PD. Analysis of cell viability by the MTT assay. Cold Spring Harb Protoc. 2018;2018:469–71.10.1101/pdb.prot095505Search in Google Scholar PubMed

[46] Tang D, Geng L, Ma J. lncRNA PROX1-AS1 mediates the migration and invasion of placental trophoblast cells via the miR-211-5p/caspase-9 axis. Bioengineered. 2021 Dec;12(1):4100–10.10.1080/21655979.2021.1953213Search in Google Scholar PubMed PubMed Central

[47] Zhang N, Zhang Y, Wu B, You S, Sun Y. Role of WW domain E3 ubiquitin protein ligase 2 in modulating ubiquitination and degradation of Septin4 in oxidative stress endothelial injury. Redox Biol. 2020;30:101419.10.1016/j.redox.2019.101419Search in Google Scholar PubMed PubMed Central

[48] Tam SY, Wu VWC, Law HKW. JNK pathway mediates low oxygen level induced epithelial-mesenchymal transition and stemness maintenance in colorectal cancer cells. Cancers (Basel). 2020;12:224.10.3390/cancers12010224Search in Google Scholar PubMed PubMed Central

[49] Armaly Z, Zaher M, Knaneh S, Abassi Z. Preeclampsia: pathogenesis and mechanisms based therapeutic approaches. Harefuah. 2019;158:742–7.Search in Google Scholar

[50] Kawasaki K, Kondoh E, Chigusa Y, Kawamura Y, Mogami H, Takeda S, et al. Metabolomic profiles of placenta in preeclampsia. Hypertension. 2019;73:671–9.10.1161/HYPERTENSIONAHA.118.12389Search in Google Scholar PubMed

[51] Suo M, Sun Y, Yang H, Ji J, He Y, Dong L, et al. miR-183-5p suppressed the invasion and migration of HTR-8/SVneo trophoblast cells partly via targeting MMP-9 in preeclampsia. Biosci Rep. 2020;40:BSR20192575.10.1042/BSR20192575Search in Google Scholar PubMed PubMed Central

[52] Ding GC, Chen M, Wang YX, Rui C, Xu W, Ding HJ, et al. MicroRNA-128a-induced apoptosis in HTR-8/SVneo trophoblast cells contributes to pre-eclampsia. Biomed Pharmacother. 2016;81:63–70.10.1016/j.biopha.2016.03.040Search in Google Scholar PubMed

[53] Sun M, Na Q, Huang L, Song G, Jin F, Li Y, et al. YAP Is decreased in preeclampsia and regulates invasion and apoptosis of HTR-8/SVneo. Reprod Sci. 2018;25:1382–93.10.1177/1933719117746784Search in Google Scholar PubMed

[54] Paraskevopoulou MD, Hatzigeorgiou AG. Analyzing MiRNA-LncRNA Interactions. Methods Mol Biol. 2016;1402:271–86.10.1007/978-1-4939-3378-5_21Search in Google Scholar PubMed

[55] He W, Li X, Xu S, Ai J, Gong Y, Gregg JL, et al. Aberrant methylation and loss of CADM2 tumor suppressor expression is associated with human renal cell carcinoma tumor progression. Biochem Biophys Res Commun. 2013;435:526–32.10.1016/j.bbrc.2013.04.074Search in Google Scholar PubMed

[56] Mavreli D, Lykoudi A, Lambrou G, Papaioannou G, Vrachnis N, Kalantaridou S, et al. Deep sequencing identified dysregulated circulating MicroRNAs in late onset preeclampsia. Vivo. 2020;34:2317–24.10.21873/invivo.12044Search in Google Scholar PubMed PubMed Central

[57] Hromadnikova I, Dvorakova L, Kotlabova K, Krofta L. The prediction of gestational hypertension, preeclampsia and fetal growth restriction via the first trimester screening of plasma exosomal C19MC microRNAs. Int J Mol Sci. 2019;20:2972.10.3390/ijms20122972Search in Google Scholar PubMed PubMed Central

[58] Hromadnikova I, Kotlabova K, Doucha J, Dlouha K, Krofta L. Absolute and relative quantification of placenta-specific micrornas in maternal circulation with placental insufficiency-related complications. J Mol Diagn. 2012;14:160–7.10.1016/j.jmoldx.2011.11.003Search in Google Scholar PubMed

Received: 2022-05-11
Revised: 2022-09-30
Accepted: 2022-10-10
Published Online: 2022-12-06

© 2022 the author(s), published by De Gruyter

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

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  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
https://doi.org/10.1515/med-2022-0595
Keywords for this article
preeclampsia; placental trophoblasts; WT1 antisense RNA; microRNA-186-5p/cell adhesion molecule 2 axis
Creative Commons
BY 4.0

Articles in the same Issue

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  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
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  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
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  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
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  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
  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
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