Startseite Medizin miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
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miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1

  • Li-Juan Zhang , Fang Wang , Pei-Yan Qi , Wei-Yan Zhou und Bing Wang EMAIL logo
Veröffentlicht/Copyright: 9. September 2021

Abstract

MicroRNAs are involved in the pathogenesis of various human malignant tumors. This study aims to explore the role of miR-513b-5p in the malignant proliferation of retinoblastoma (RB) cells and its potential molecular mechanisms. The function-gain and function-loss experiments were performed in Weri-RB1 cells using miR-513b-5 mimics and inhibitors. miR-513b-5p mimics inhibited the proliferation and clone formation and promoted apoptosis of Weri-RB1 cells. In contrast, the miR-513b-5p inhibitor promoted the proliferation and clone formation of Weri-RB1 cells and inhibited cell apoptosis. miR-513b-5p can directly bind to the 3′UTR region of TRIB1 mRNA, and inhibit its protein expression. Overexpression of TRIB1 promoted the proliferation and cloning of Weri-RB1 cells but inhibited their apoptosis. The knockdown of TRIB1 inhibited the proliferation and clone formation of Weri-RB1 cells and promoted cell apoptosis. In addition, miR-513b-5p mimics neutralized the effects of TRIB1 overexpression on the proliferation and apoptosis of Weri-RB1 cells. Finally, miR-513b-5p can inhibit the phosphorylation level of AKT, mTOR, and p70, while TRIB1 played the opposite role. miR-513b-5p inhibits the malignant proliferation of Weri-RB1 cells by repressing the expression of TRIB1. miR-513b-5p and TRIB1 may be the biomarkers and/or key targets for clinical diagnosis and treatment of RB.

1 Introduction

Retinoblastoma (RB) is the most common intraocular malignant tumor in infants, which seriously endangers their visual function and life. It accounts for 2.5–4% of malignant tumors in children, with a prevalence of 1/20,000 to 1/15,000 [1,2]. In recent years, with the continuous improvement of the diagnosis and treatment methods, the prognosis and survival rate of RB patients have been improved. However, the pathogenic factors and molecular mechanisms of the disease have not been fully studied. Therefore, further research and exploration of genes and action mechanism that related to the occurrence and development of RB are of great significance [3].

MicroRNAs (miRNAs) are a group of endogenous non-coding RNA molecules with a length of 20–22 nucleotides [4]. They can directly interact with the 3′-non-translation regions (3′UTR) of the target mRNA, leading to mRNA degradation or translation inhibition, thereby negatively regulating the expression of the target genes [5]. miRNAs have an important relationship with the occurrence and development of cancer [6]. Many different miRNA abnormalities have been identified in RB. Their abnormal expression plays an important role in various processes of cancer, including cell proliferation, metastasis, apoptosis, invasion, epithelial–mesenchymal transformation, and angiogenesis [7].

Previous studies have shown that miR-513b-5p can play a unique role in different types of solid tumors. For example, the expression of miR-513b-5p is significantly downregulated in non-small cell lung cancer (NSCLC) [8,9] and gastric cancer [10]. Its exogenous overexpression can significantly inhibit the proliferation, invasion, migration, and promote apoptosis of NSCLC [8,9] and gastric cancer cells [10]. However, some studies have also reported that miR-513b-5p plays an oncogene in cervical cancer [11] and ovarian cancer [12]. In addition, miR-513b-5p has also been identified to play an important role in testicular development and male sexual maturation [13,14]. However, the role of mir-513b-5p in RB generation has not been reported.

The aim of this study was to investigate the effect of miR-513b-5p overexpression and downexpression on the proliferation and apoptosis of RB cells and its possible mechanism. The results may provide some new insights into the pathogenesis of RB and help to explore new treatments.

2 Materials and methods

2.1 Cell culture

The retinoblastoma cell line Weri-RB-1 and 293 T cell were obtained from the American Type Culture Collection (ATCC), and cultured in the Dulbecco’s modified Eagle’s medium (DMEM; Gibco; Thermo Fisher Scientific, Inc.) with 10% FBS, 100 U/mL penicillin, and 0.1 mg/mL streptomycin at 37°C with the atmosphere of 5% CO2.

2.2 Cell transfection

miR-513b-5p mimics, miR-513b-5p inhibitor, siRNA specifically targeting TRIB1 (TRIB1-KD), TRIB1 overexpression plasmid (TRIB1-OE), and their respective negative control (NC) were obtained from GenePharma Co. Ltd. (Shanghai, China). Transfection was performed according to the instructions of the Lipofectamine2000 transfection kit (Invitrogen; Thermo Fisher Scientific, Inc.).

2.3 Cell Counting Kit‑8 (CCK-8) assay

The transfected cells were seeded into a 96-well plate at a concentration of 1 × 10³ cells per well. After culturing for 24, 48, and 72 h, the old medium in each well was removed, and fresh DMEM containing 10% CCK8 reagent (Beyotime Institute of Biotechnology) was added and incubated at 37°C for 2 h. Subsequently, the absorbance value (OD) of each well was detected with a microplate reader at a wavelength of 450 nm.

2.4 Clone formation assay

The transfected cells were seeded in a 6-well plate and cultured for 1–2 weeks until the clones were visible. The medium was removed, and the cells were carefully washed twice with 2 mL of PBS. After the PBS was air-dried, the clones were fixed with 4% paraformaldehyde for 30 min at room temperature and then stained with 0.1% crystal violet dye for 30 min at room temperature. After dyeing, the dye was cleaned and then the number of clones was counted.

2.5 Flow cytometric analysis of apoptosis

The apoptosis of Weri-RB1 cells was evaluated by using an Annexin V-FITC Apoptosis Detection Kit (BD Biosciences) and PI staining according to the manufacturer’s instructions. After 48 h of transfection, the cells were digested with trypsin without EDTA, and centrifuged at 3,000g for 5 min at room temperature. About 3 mL PBS was added to resuspend and wash the cell precipitation. Subsequently, the cells were centrifuged at 3,000g for another 5 min at room temperature. 1× binding buffer was added to resuspend the cells, and the cell density was adjusted to 1–5 × 106/mL. About 100 μL of the cell suspension was added into a 5 mL flow cytometry tube, and mixed with 5 μL Annexin V/FITC, and incubated in the dark for 5 min at room temperature. Then, 10 μL of the PI dye solution and 400 μL of PBS was added, and the apoptosis of Weri-RB1 cells in each group was analyzed by flow cytometer (FACS Calibur; BD Biosciences, Franklin Lakes, NJ). FlowJo software was used to analyze the flow cytometry outcomes.

2.6 Western blot analysis

After 48 h of transfection, the cells were lysed with RIPA lysate (Pierce, USA) in ice for 10 min, and the total protein was extracted. The concentration of protein was measured with the BCA protein assay kit (Pierce, USA). The protein samples were separated by SDS polyacrylamide gel electrophoresis and transferred into polyvinylidene difluoride membranes (PVDF; Millipore, Billerica, MA). The membranes were blocked with 5% skim milk for 1 h at room temperature and incubated overnight at 4°C with primary antibodies. The primary antibodies are as follows: anti-Bax (50599-2-Ig), anti-Bcl2 (12789-1-AP), anti-caspase3 (19677-1-AP), anti-p53 (60283-2-Ig), anti-GAPDH (60004-1-Ig), anti-AKT (10176-2-AP), anti-p-AKT (Ser473, 66444-1-Ig), anti-mTOR (66888-1-Ig), and anti-p-mTOR (Ser2448, 66888-1-Ig) were obtained from PTG, and anti-p70 (ab184551), anti-p-p70 (Ser371, ab109393), and anti-TRIB1 (ab137717) were obtained from Abcam. Following this, the secondary antibody (HRP-conjugated Goat Anti-Rabbit IgG, SA00001-2; and HRP-conjugated Goat Anti-Mouse IgG, SA00001-1, PTG) was applied and incubated with the membrane for 1 h at room temperature. Finally, the proteins were visualized with enhanced chemiluminescence reagents (Pierce, USA). The QUANTITY ONE software (Bio-Rad Laboratories, Inc.) was used to scan and calculate the relative expression quantity of each protein.

2.7 Double luciferase assay

The TRIB1 3′UTR region was cloned into the pmiR GLO vector, and the binding region of TRIB1 3′UTR to miR-513b-5p was mutated. TRIB1-3′UTR-WT and TRIB1-3′UTR-MUT plasmids were constructed and co-transfected into 293T cells with a miR-513b-5p mimics or negative control (NC) using Lipofectamine 2000 (Invitrogen), respectively. After 48 h, the Dual Luciferase Assay System Kit (Promega, WI, USA) was employed to analyze the activity of the luciferase.

2.8 Statistical analysis

GraphPad Prism 6.0 was used for data analysis (GraphPad Software Inc., San Diego, CA). All data were presented as the mean ± standard error of the mean (SEM). The differences were evaluated using one-way ANOVA followed by Tukey’s post hoc test for multiple comparisons and the Mann–Whitney U-test for pair-wise comparisons. A P-value less than 0.05 was considered to indicate a statistically significant difference.

3 Results

3.1 miR-513b-5p inhibits the proliferation of Weri-RB1 cells in vitro

In order to investigate the role of miR-513b-5p on the proliferation of Weri-RB1 cells, CCK-8 and clone formation assays were performed. The results of the CCK-8 assay showed that compared with the NC group, miR-513b-5p mimics inhibited the proliferation of Weri-RB1 cells, while the miR-513b-5p inhibitor promoted cell proliferation (Figure 1a, P < 0.05). In addition, the results of the clone formation experiment were consistent with the results of the CCK-8 assay. The number of cell clones formed in the miR-513b-5p mimics group was significantly lower than that in the NC group, while the clone numbers in the miR-513b-5p inhibitor group were decreased (Figure 1b, P < 0.05).

Figure 1 
                  miR-513b-5p inhibits the proliferation and promotes the apoptosis of Weri-RB1 cells in vitro. The role of miR-513b-5p mimics and inhibitors in the proliferation, clone formation, and apoptosis of Weri-RB1 cells was detected by CCK-8 (a), clone formation (b), and flow cytometry (c and d) assays. The differences were evaluated using the Mann–Whitney U-test for pair-wise comparisons. *P < 0.05. Each group of a includes six samples, each group of b–d includes three samples. All experiments were repeated three times independently, and the individual experiments were performed 1 week apart.
Figure 1

miR-513b-5p inhibits the proliferation and promotes the apoptosis of Weri-RB1 cells in vitro. The role of miR-513b-5p mimics and inhibitors in the proliferation, clone formation, and apoptosis of Weri-RB1 cells was detected by CCK-8 (a), clone formation (b), and flow cytometry (c and d) assays. The differences were evaluated using the Mann–Whitney U-test for pair-wise comparisons. *P < 0.05. Each group of a includes six samples, each group of b–d includes three samples. All experiments were repeated three times independently, and the individual experiments were performed 1 week apart.

3.2 miR-513b-5p promotes the apoptosis of Weri-RB1 cells in vitro

The role of miR-513b-5p on the apoptosis of Weri-RB1 cells was detected using flow cytometry and western blot. The results showed that the apoptosis ratio in the miR-513b-5p mimics group was significantly higher than that in the NC group, while the apoptosis ratio in the miR-513b-5p inhibitor group was decreased (Figure 1c and d, P < 0.05). In addition, after miR-513b-5p mimics were transfected, the protein level of anti-apoptotic protein Bcl2 was decreased, while the protein level of pro-apoptotic protein Bax, cleaved-caspase3, and p53 was increased (Figure 2a and b, P < 0.05). Furthermore, after transfection of miR-513b-5p inhibitor, the expression of anti-apoptotic protein Bcl2 increased, and the expression of pro-apoptotic protein Bax, cleaved-caspase3, and p53 decreased (Figure 2a and b, P < 0.05).

Figure 2 
                  miR-513b-5p inhibits the activation of the AKT/mTOR signaling pathway. (a and b) The protein expression of key proteins related to apoptosis was measured using a western blot. (c and d) The protein expression of key proteins in the AKT/mTOR signaling pathway was measured using western blot. The differences were evaluated using the Mann–Whitney U-test for pair-wise comparisons. *P < 0.05. Each group of (b and d) includes three samples. All experiments were repeated three times independently, and the individual experiments were performed 1 week apart.
Figure 2

miR-513b-5p inhibits the activation of the AKT/mTOR signaling pathway. (a and b) The protein expression of key proteins related to apoptosis was measured using a western blot. (c and d) The protein expression of key proteins in the AKT/mTOR signaling pathway was measured using western blot. The differences were evaluated using the Mann–Whitney U-test for pair-wise comparisons. *P < 0.05. Each group of (b and d) includes three samples. All experiments were repeated three times independently, and the individual experiments were performed 1 week apart.

3.3 miR-513b-5p inhibits the activation of the AKT/mTOR signaling pathway

The effect of miR-513b-5p on the AKT/mTOR signaling pathway activation was determined by western blot. The results showed that miR-513b-5p mimics inhibited the phosphorylation of AKT, mTOR, and p70 (Figure 2c and d, P < 0.05). In contrast, the miR-513b-5p inhibitor increased the phosphorylation levels of AKT, mTOR, and p70 (Figure 2c and d, P < 0.05).

3.4 miR-513b-5p can bind to TRIB1 mRNA and regulate its protein expression

The TargetScan software predicted the direct binding site of miR-513b-5p and 3′UTR region of TRIB1 mRNA (Figure 3a). Subsequently, the direct binding of miR-513b-5p to the 3′UTR region of TRIB1 mRNA was determined by using a double-luciferase assay. As shown in Figure 3b, the co-transfection of miR-513b-5p mimics and pmiR-GLO-TRIB1-3′UTR-WT recombinant plasmid significantly reduced the expression of luciferase, while the co-transfection of miR-513b-5p mimics and pmiR-GLO-TRIB1-3′UTR-MUT recombinant plasmid did not significantly affect the level of luciferase. This result revealed that miR-513b-5p could directly bind to the 3′UTR region of the TRIB1 mRNA through the predicted site. In addition, the miR-513b-5p mimic inhibited the protein expression of TRIB1, while the miR-513b-5p inhibitor up-regulated the expression of the TRIB1 protein (Figure 3c and d, P < 0.05). In summary, miR-513b-5p can bind to the 3′UTR region of TRIB1 mRNA and regulate its protein expression.

Figure 3 
                  miR-513b-5p can bind to TRIB1 mRNA and regulate its protein expression. (a) The TargetScan software predicted the direct binding site of miR-513b-5p and the 3′UTR region of TRIB1 mRNA. (b) The relative expression of luciferase and direct binding of miR-513b-5p to the 3′UTR region of TRIB1 mRNA was determined by using a double-luciferase assay. (c and d) The protein expression of TRIB1 was measured using a western blot. The differences of (b) were evaluated using one-way ANOVA followed by Tukey’s post hoc test, and the Mann–Whitney U-test for (d). *P < 0.05. Each group of (b and d) includes three samples. All experiments were repeated three times independently, and the individual experiments were performed 1 week apart.
Figure 3

miR-513b-5p can bind to TRIB1 mRNA and regulate its protein expression. (a) The TargetScan software predicted the direct binding site of miR-513b-5p and the 3′UTR region of TRIB1 mRNA. (b) The relative expression of luciferase and direct binding of miR-513b-5p to the 3′UTR region of TRIB1 mRNA was determined by using a double-luciferase assay. (c and d) The protein expression of TRIB1 was measured using a western blot. The differences of (b) were evaluated using one-way ANOVA followed by Tukey’s post hoc test, and the Mann–Whitney U-test for (d). *P < 0.05. Each group of (b and d) includes three samples. All experiments were repeated three times independently, and the individual experiments were performed 1 week apart.

3.5 TRIB1 promotes the proliferation and inhibits the apoptosis of Weri-RB1 cells in vitro

The effect of TRIB1 on the proliferation and apoptosis of Weri-RB1 cells was determined. As shown in Figure 4a and b, the overexpression of TRIB1 (TRIB1-OE) promoted the proliferation and clone formation of Weri-RB1 cells, while the knockdown of TRIB1 (TRIB1-KD) inhibited the proliferation and clone formation of Weri-RB1 cells. In addition, the overexpression of TRIB1 inhibited the apoptosis of Weri- RB1 cells (Figure 4c and d), upregulated the protein expression of Bcl2, and downregulated the protein expression of cleaved-caspase3 and p53 (Figure 5a and b). The knockdown of TRIB1 induced apoptosis of Weri-RB1 cells (Figure 4c and d), downregulated the protein expression of Bcl2 and upregulated the protein expression of cleaved-caspase3 and p53 (Figure 5a and b). Furthermore, the miR-513b-5p mimic could neutralize the role of TRIB1 overexpression on the proliferation and apoptosis of Weri-rb1 cells (Figures 4a5b, P < 0.05).

Figure 4 
                  TRIB1 promotes proliferation and inhibits the apoptosis of Weri-RB1 cells in vitro. The role of TRIB1 overexpression (TRIB1-OE) and TRIB1 knockdown (TRIB1-KD) in the proliferation, clone formation, and apoptosis of Weri-RB1 cells was detected by CCK-8 (a), clone formation (b), and flow cytometry (c and d) assays. The differences were evaluated using the Mann–Whitney U-test for pair-wise comparisons. *P < 0.05, compared to NC; #
                     P < 0.05, compared to TRIB1-OE. Each group of (a) includes six samples, each group of (b and d) includes three samples. All experiments were repeated three times independently, and the individual experiments were performed 1 week apart.
Figure 4

TRIB1 promotes proliferation and inhibits the apoptosis of Weri-RB1 cells in vitro. The role of TRIB1 overexpression (TRIB1-OE) and TRIB1 knockdown (TRIB1-KD) in the proliferation, clone formation, and apoptosis of Weri-RB1 cells was detected by CCK-8 (a), clone formation (b), and flow cytometry (c and d) assays. The differences were evaluated using the Mann–Whitney U-test for pair-wise comparisons. *P < 0.05, compared to NC; # P < 0.05, compared to TRIB1-OE. Each group of (a) includes six samples, each group of (b and d) includes three samples. All experiments were repeated three times independently, and the individual experiments were performed 1 week apart.

Figure 5 
                  TRIB1 promotes the activation of the AKT/mTOR signaling pathway. (a and b) The protein expression of key proteins related to apoptosis was measured using western blot. (c and d) The protein expression of key proteins in the AKT/mTOR signaling pathway was measured using western blot. The differences were evaluated using the Mann–Whitney U-test for pair-wise comparisons. *P < 0.05, compared to NC; #
                     P < 0.05, compared to TRIB1-OE. Each group of (b and d) includes three samples. All experiments were repeated three times independently, and the individual experiments were performed 1 week apart.
Figure 5

TRIB1 promotes the activation of the AKT/mTOR signaling pathway. (a and b) The protein expression of key proteins related to apoptosis was measured using western blot. (c and d) The protein expression of key proteins in the AKT/mTOR signaling pathway was measured using western blot. The differences were evaluated using the Mann–Whitney U-test for pair-wise comparisons. *P < 0.05, compared to NC; # P < 0.05, compared to TRIB1-OE. Each group of (b and d) includes three samples. All experiments were repeated three times independently, and the individual experiments were performed 1 week apart.

In addition, the overexpression of TRIB1 promoted the phosphorylation of AKT and mTOR, while the knockdown of TRIB1 decreased the phosphorylation levels of AKT and mTOR (Figure 5c and d, P < 0.05). Furthermore, miR-513b-5p can counteract the effect of TRIB1 overexpression on the AKT and mTOR phosphorylation (Figure 5c and d, P < 0.05).

4 Discussion

RB is a malignant ocular tumor in infants with a high blindness rate. In China, approximately 1,000 children are diagnosed with RB every year [15]. Moreover, about 5% of children’s blindness is caused by RB [16]. Therefore, it is of great significance to investigate the pathogenesis and therapeutic targets of RB.

It is well known that miRNAs are involved in the pathogenesis of various human malignancies. In this study, we found that miR-513b-5p inhibited the proliferation and promoted apoptosis of Weri-RB1 cells in vitro. The results of this research are consistent with previous studies on the role of miR-513b-5p in NSCLC [8], embryonic testicular cancer [13], gastric cancer [10], and osteosarcoma [17] cells, but are contrary to the role of miR-513b-5p in cervical cancer [11] and ovarian cancer [12]. This may be due to the uniqueness of the tumor type.

TRIB1 (tribbles homologue 1) is a member of the Tribbles family, which is initially found to modulate string/cdc25 in Drosophila morphogenesis [18]. TRIB1 has been reported to be associated with the occurrence and development of a variety of tumors, including leukemia [19], hepatocellular carcinoma [20], colorectal cancer [21], and prostate cancer [22]. It has been revealed that TRIB1 is highly expressed in prostate cancer and follicular thyroid cancer, and promotes the proliferation, survival, and tumor growth of cancer cells. In this article, we determined that TRIB1 is the direct binding target of miR-513b-5p and detected that its overexpression contributed to the proliferation and cloning of Weri-RB11 cells, but inhibited their apoptosis. Our findings are consistent with prevenient conclusions about the role of TRIB1 in malignancies, suggesting that TRIB1 may be an oncogene.

The dual-luciferase assay confirmed that TRIB1 is the direct binding target of miR-513b-5p. In addition, the results of western blot showed that miR-513b-5p inhibited the protein expression of TRIB1. Meanwhile, this study also clarified that miR-513b-5p/TRIB1 can regulate the phosphorylation of the PI3K signaling pathway. The overexpression of miR-513b-5p inhibited the phosphorylation of AKT, mTOR, and p70, while TRIB1 played the opposite role. However, there are many shortcomings in our experiment, such as the lack of in vivo experiments and the relatively single target and action mechanism. Further studies will be conducted.

In conclusion, our study suggested that miR-513b-5p inhibited the expression of TRIB1 and exerted a tumor suppressor gene in Weri-RB1 cells. We demonstrated for the first time the role and the interaction of miR-513b-5p and TRIB1 in Weri-RB1 cells. It is speculated that miR-513b-5p and TRIB1 may be the biomarkers and/or key targets for clinical diagnosis and treatment of RB in the future.

  1. Funding information: This article has received financial support from the Jinan City Clinical Medicine Science and Technology Innovation Plan (201907078) and the Shandong Medicine and Health Science and Technology Development Plan (2019WS499).

  2. Conflict of interest: The authors declare that they have no competing interests, and all authors should confirm its accuracy.

  3. Data availability statements: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2021-03-23
Revised: 2021-08-12
Accepted: 2021-08-12
Published Online: 2021-09-09

© 2021 Li-Juan Zhang et al., published by De Gruyter

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

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  31. Correlation between kinematic sagittal parameters of the cervical lordosis or head posture and disc degeneration in patients with posterior neck pain
  32. Review Articles
  33. Hepatoid adenocarcinoma of the lung: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database
  34. Research Articles
  35. Thermography in the diagnosis of carpal tunnel syndrome
  36. Pemetrexed-based first-line chemotherapy had particularly prominent objective response rate for advanced NSCLC: A network meta-analysis
  37. Comparison of single and double autologous stem cell transplantation in multiple myeloma patients
  38. The influence of smoking in minimally invasive spinal fusion surgery
  39. Impact of body mass index on left atrial dimension in HOCM patients
  40. Expression and clinical significance of CMTM1 in hepatocellular carcinoma
  41. miR-142-5p promotes cervical cancer progression by targeting LMX1A through Wnt/β-catenin pathway
  42. Comparison of multiple flatfoot indicators in 5–8-year-old children
  43. Early MRI imaging and follow-up study in cerebral amyloid angiopathy
  44. Intestinal fatty acid-binding protein as a biomarker for the diagnosis of strangulated intestinal obstruction: A meta-analysis
  45. miR-128-3p inhibits apoptosis and inflammation in LPS-induced sepsis by targeting TGFBR2
  46. Dynamic perfusion CT – A promising tool to diagnose pancreatic ductal adenocarcinoma
  47. Biomechanical evaluation of self-cinching stitch techniques in rotator cuff repair: The single-loop and double-loop knot stitches
  48. Review Articles
  49. The ambiguous role of mannose-binding lectin (MBL) in human immunity
  50. Case Report
  51. Membranous nephropathy with pulmonary cryptococcosis with improved 1-year follow-up results: A case report
  52. Fertility problems in males carrying an inversion of chromosome 10
  53. Acute myeloid leukemia with leukemic pleural effusion and high levels of pleural adenosine deaminase: A case report and review of literature
  54. Metastatic renal Ewing’s sarcoma in adult woman: Case report and review of the literature
  55. Burkitt-like lymphoma with 11q aberration in a patient with AIDS and a patient without AIDS: Two cases reports and literature review
  56. Skull hemophilia pseudotumor: A case report
  57. Judicious use of low-dosage corticosteroids for non-severe COVID-19: A case report
  58. Adult-onset citrullinaemia type II with liver cirrhosis: A rare cause of hyperammonaemia
  59. Clinicopathologic features of Good’s syndrome: Two cases and literature review
  60. Fatal immune-related hepatitis with intrahepatic cholestasis and pneumonia associated with camrelizumab: A case report and literature review
  61. Research Articles
  62. Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study
  63. Significance of nucleic acid positive anal swab in COVID-19 patients
  64. circAPLP2 promotes colorectal cancer progression by upregulating HELLS by targeting miR-335-5p
  65. Ratios between circulating myeloid cells and lymphocytes are associated with mortality in severe COVID-19 patients
  66. Risk factors of left atrial appendage thrombus in patients with non-valvular atrial fibrillation
  67. Clinical features of hypertensive patients with COVID-19 compared with a normotensive group: Single-center experience in China
  68. Surgical myocardial revascularization outcomes in Kawasaki disease: systematic review and meta-analysis
  69. Decreased chromobox homologue 7 expression is associated with epithelial–mesenchymal transition and poor prognosis in cervical cancer
  70. FGF16 regulated by miR-520b enhances the cell proliferation of lung cancer
  71. Platelet-rich fibrin: Basics of biological actions and protocol modifications
  72. Accurate diagnosis of prostate cancer using logistic regression
  73. miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus
  74. Prognostic significance of TRIM28 expression in patients with breast carcinoma
  75. Integrative bioinformatics analysis of KPNA2 in six major human cancers
  76. Exosomal-mediated transfer of OIP5-AS1 enhanced cell chemoresistance to trastuzumab in breast cancer via up-regulating HMGB3 by sponging miR-381-3p
  77. A four-lncRNA signature for predicting prognosis of recurrence patients with gastric cancer
  78. Knockdown of circ_0003204 alleviates oxidative low-density lipoprotein-induced human umbilical vein endothelial cells injury: Circulating RNAs could explain atherosclerosis disease progression
  79. Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway
  80. Knockdown of lncRNA TapSAKI alleviates LPS-induced injury in HK-2 cells through the miR-205/IRF3 pathway
  81. COVID-19 severity in relation to sociodemographics and vitamin D use
  82. Clinical analysis of 11 cases of nocardiosis
  83. Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
  84. Four long noncoding RNAs act as biomarkers in lung adenocarcinoma
  85. Real-world evidence of cytomegalovirus reactivation in non-Hodgkin lymphomas treated with bendamustine-containing regimens
  86. Relation between IL-8 level and obstructive sleep apnea syndrome
  87. circAGFG1 sponges miR-28-5p to promote non-small-cell lung cancer progression through modulating HIF-1α level
  88. Nomogram prediction model for renal anaemia in IgA nephropathy patients
  89. Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis
  90. NDRG2 inhibition facilitates angiogenesis of hepatocellular carcinoma
  91. A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1
  92. Clinical and prognostic features of MMP-2 and VEGF in AEG patients
  93. The value of miR-510 in the prognosis and development of colon cancer
  94. Functional implications of PABPC1 in the development of ovarian cancer
  95. Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy
  96. Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis
  97. Prediction of improvement after anterior cruciate ligament reconstruction
  98. Effluent Osteopontin levels reflect the peritoneal solute transport rate
  99. circ_0038467 promotes PM2.5-induced bronchial epithelial cell dysfunction
  100. Significance of miR-141 and miR-340 in cervical squamous cell carcinoma
  101. Association between hair cortisol concentration and metabolic syndrome
  102. Microvessel density as a prognostic indicator of prostate cancer: A systematic review and meta-analysis
  103. Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia
  104. Knee alterations in rheumatoid arthritis: Comparison of US and MRI
  105. Long non-coding RNA TUG1 aggravates cerebral ischemia and reperfusion injury by sponging miR-493-3p/miR-410-3p
  106. lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p
  107. Development and validation of a nomogram for predicting severity in patients with hemorrhagic fever with renal syndrome: A retrospective study
  108. Analysis of COVID-19 outbreak origin in China in 2019 using differentiation method for unusual epidemiological events
  109. Laparoscopic versus open major liver resection for hepatocellular carcinoma: A case-matched analysis of short- and long-term outcomes
  110. Travelers’ vaccines and their adverse events in Nara, Japan
  111. Association between Tfh and PGA in children with Henoch–Schönlein purpura
  112. Can exchange transfusion be replaced by double-LED phototherapy?
  113. circ_0005962 functions as an oncogene to aggravate NSCLC progression
  114. Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells
  115. Serum intact fibroblast growth factor 23 in healthy paediatric population
  116. Algorithm of rational approach to reconstruction in Fournier’s disease
  117. A meta-analysis of exosome in the treatment of spinal cord injury
  118. Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma
  119. Dexmedetomidine may decrease the bupivacaine toxicity to heart
  120. Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression
  121. Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p
  122. External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients
  123. miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12
  124. HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis
  125. Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient’s prognosis
  126. Cell population data in identifying active tuberculosis and community-acquired pneumonia
  127. Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression
  128. Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis
  129. 3D-printed porous scaffold promotes osteogenic differentiation of hADMSCs
  130. Association of gene polymorphisms with women urinary incontinence
  131. Influence of COVID-19 pandemic on stress levels of urologic patients
  132. miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer
  133. miR-519d downregulates LEP expression to inhibit preeclampsia development
  134. Comparison of single- and triple-port VATS for lung cancer: A meta-analysis
  135. Fluorescent light energy modulates healing in skin grafted mouse model
  136. Silencing CDK6-AS1 inhibits LPS-induced inflammatory damage in HK-2 cells
  137. Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC
  138. Severe postoperative hyperbilirubinemia in congenital heart disease
  139. Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway
  140. Clinical factors predicting ureteral stent failure in patients with external ureteral compression
  141. Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
  142. Triple-Endobutton and clavicular hook: A propensity score matching analysis
  143. Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
  144. Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
  145. miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
  146. Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
  147. The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
  148. Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
  149. No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
  150. circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
  151. Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
  152. Educational program for orthopedic surgeons’ influences for osteoporosis
  153. Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
  154. GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
  155. lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
  156. Anticoagulation is the answer in treating noncritical COVID-19 patients
  157. Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
  158. Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
  159. VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
  160. Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
  161. Treatment of osteoporosis with teriparatide: The Slovenian experience
  162. New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
  163. Superenhancer–transcription factor regulatory network in malignant tumors
  164. β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
  165. Clinical features of atypical tuberculosis mimicking bacterial pneumonia
  166. Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
  167. Effect of electromagnetic field on abortion: A systematic review and meta-analysis
  168. miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1
  169. MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
  170. Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
  171. miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
  172. Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
  173. MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
  174. Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
  175. circATP2A2 promotes osteosarcoma progression by upregulating MYH9
  176. Prognostic role of oxytocin receptor in colon adenocarcinoma
  177. Review Articles
  178. The function of non-coding RNAs in idiopathic pulmonary fibrosis
  179. Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
  180. Role of cesarean section in the development of neonatal gut microbiota: A systematic review
  181. Small cell lung cancer transformation during antitumor therapies: A systematic review
  182. Research progress of gut microbiota and frailty syndrome
  183. Recommendations for outpatient activity in COVID-19 pandemic
  184. Rapid Communication
  185. Disparity in clinical characteristics between 2019 novel coronavirus pneumonia and leptospirosis
  186. Use of microspheres in embolization for unruptured renal angiomyolipomas
  187. COVID-19 cases with delayed absorption of lung lesion
  188. A triple combination of treatments on moderate COVID-19
  189. Social networks and eating disorders during the Covid-19 pandemic
  190. Letter
  191. COVID-19, WHO guidelines, pedagogy, and respite
  192. Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
  193. COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
  194. What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
  195. Case Report
  196. Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature
  197. CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
  198. Synchronous primary malignancy of colon cancer and mantle cell lymphoma: A case report
  199. Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review
  200. Persistent SARS-CoV-2-positive over 4 months in a COVID-19 patient with CHB
  201. Pulmonary parenchymal involvement caused by Tropheryma whipplei
  202. Mediastinal mixed germ cell tumor: A case report and literature review
  203. Ovarian female adnexal tumor of probable Wolffian origin – Case report
  204. Rare paratesticular aggressive angiomyxoma mimicking an epididymal tumor in an 82-year-old man: Case report
  205. Perimenopausal giant hydatidiform mole complicated with preeclampsia and hyperthyroidism: A case report and literature review
  206. Primary orbital ganglioneuroblastoma: A case report
  207. Primary aortic intimal sarcoma masquerading as intramural hematoma
  208. Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review
  209. Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature
  210. Chondroblastoma of mandibular condyle: Case report and literature review
  211. Trauma-induced complete pacemaker lead fracture 8 months prior to hospitalization: A case report
  212. Primary intradural extramedullary extraosseous Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) of the thoracolumbar spine: A case report and literature review
  213. Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
  214. High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
  215. Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
  216. Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
  217. Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
  218. Retraction
  219. Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
  220. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
  221. An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
  222. Breast cancer recurrence prediction with ensemble methods and cost-sensitive learning
Heruntergeladen am 30.12.2025 von https://www.degruyterbrill.com/document/doi/10.1515/med-2021-0343/html
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