Transforming growth factor-ß1-induced podocyte injury is associated with increased microRNA-155 expression, enhanced inflammatory responses and MAPK pathway activation.

MicroRNA-155 (miR-155) is associated with various diseases. However, the potential role of miR-155 in early glomerular disease (EGD) remains elusive. In the present study, the clinical significance of urinary miR-155 expression was explored in patients with EGD using receiver operating characteristic curve analysis. Conditionally immortalized mouse podocytes were cultured in vitro and treated with transforming growth factor-ß1 (TGF-ß1) at different concentrations and durations. The gene expression levels of mRNAs and miR-155 were detected using reverse transcription-quantitative PCR. Synaptopodin, CD2-associated protein (CD2AP), p38, and extracellular signal-regulated kinase (Erk) 1/2 expressions were detected using western blotting. Cell supernatants were collected for assaying tumor necrosis factor (TNF)-α and interleukin (IL)-6 concentrations using enzyme-linked immunosorbent assay. The Pearson correlation analysis was used to analyze the correlation between miR-155 levels and TNF-α or IL-6. It was found that miR-155 levels in urine have high sensitivity and specificity in the diagnosis of EGD. Time- and dose-dependent TGF-ß1 treatments downregulated synaptopodin and CD2AP expression levels, and activated the p38 and Erk 1/2 pathway. However, these effects were attenuated by p38 and Erk 1/2 phosphorylation inhibitors. Additionally, TNF-α and IL-6 secretions were elevated, and their concentrations were positively correlated with the expression of miR-155 during podocyte injury. Thus, the present study indicated that miR-155 is a potential biomarker for the diagnosis of EGD, and its expression is associated with the release of pro-inflammatory cytokines and activation of mitogen-activated protein kinase (MAPK) pathway in TGF-ß1-induced podocyte injury. The present study suggests that the TGF-ß1/miR-155/MAPK axis is a novel target in the mechanism of EGD.

Tacrolimus versus cyclophosphamide for patients with idiopathic membranous nephropathy and treated with steroids: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The therapeutic effects of tacrolimus (TAC) versus cyclophosphamide (CTX) were not fully illustrated for patients with idiopathic membranous nephropathy (IMN). METHODS: The PubMed, EmBase, Cochrane library, and CNKI were systematically searched throughout March 2020 for randomized controlled trials evaluating the therapeutic effects of TAC versus CTX for IMN patients treated with steroids. The pooled relative risks (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using the random-effects model. RESULTS: Twelve trials recruited a total of 868 IMN patients were identified and contained in final meta-analysis. Patients in TAC group was associated with an increased incidence of overall remission (12 trials: 868 patients; RR: 1.21; 95% CI: 1.11-1.31; p < 0.001) and complete remission (12 trials: 868 patients; RR: 1.50; 95% CI: 1.25-1.80; p < 0.001). Moreover, we noted TAC therapy significantly reduced urinary protein excretion (9 trials: 567 patients; WMD: -1.06; 95%CI: -1.41 to -0.71; p < 0.001), and increased serum albumin (9 trials: 567 patients; WMD: 5.37; 95%CI: 2.97 to 7.77; p < 0.001) than CTX therapy. Furthermore, no significant difference between TAC and CTX for serum creatinine was detected (6 trials: 378 patients; WMD: 0.15; 95%CI: -3.46 to 3.75; p = 0.936). Finally, the risk of alopecia (p = 0.008), infection (p = 0.045), leukocytosis (p = 0.002), and elevated ALT/AST (p = 0.011) in TAC group was significantly lower than CTX group, whereas TAC was associated with an increased risk of tremor than CTX (p = 0.010). CONCLUSIONS: This study found IMN patients treated with TAC combined with steroids provides a better therapeutic effect and less adverse events than those treated with CTX combined with steroids, with moderate-certainty evidence.

Long noncoding RNA MSC-AS1 promotes hepatocellular carcinoma oncogenesis via inducing the expression of phosphoglycerate kinase 1.

BACKGROUND AND OBJECTIVES: Increasing studies report that lncRNAs are dysregulated in hepatocellular carcinoma (HCC), which might function as significant diagnostic biomarkers of HCC. LncRNA MSC-AS1 has been newly discovered in several cancers. However, its biological effect in HCC remains to be clearly elucidated. The aim of our work was to test MSC-AS1 expression level and assess its function in HCC progression. METHODS: Expression levels of MSC-AS1 and PGK1 in HCC were tested by qRT-PCR in HCC cells including HUH-7, BEL-7404, SNU449, HepG2, QGY-7701, and human normal liver cells (HL-7702 cells). Association of MSC-AS1 expression with various clinicopathological features and patients' survival were analyzed by chi-squared test and Kaplan-Meier, respectively. The functions of MSC-AS1 in HCC cells were investigated using EdU assay, colony formation, flow cytometry, would healing assay, and Transwell matrigel invasion assays. The correlation between MSC-AS1 and PGK1 was confirmed using a RIP assay. Protein expression of PGK1 was evaluated using a western blot assay. RESULTS: MSC-AS1 was obviously upregulated in HCC tissues and HCC cells. Knockdown of MSC-AS1 repressed HepG2 and BEL-7404 cell proliferation, colony formation capacity, and triggered cell apoptosis. HepG2 and BEL-7404 cell cycle was blocked in G1 phase and cell migration/invasion was remarkably depressed. Downregulation of MSC-AS1 in HCC cells reduced PGK1 expression. In vivo data demonstrated that silence of MSC-AS1 suppressed HCC development via activating PGK1. CONCLUSIONS: Taken these together, we indicated that MSC-AS1 promoted HCC oncogenesis via inducing the expression of PGK1.

Circular RNA circ_0014717 Suppresses Hepatocellular Carcinoma Tumorigenesis Through Regulating miR-668-3p/BTG2 Axis.

Recent studies have reported a close association between circRNAs and cancer development. CircRNAs have been recognized to be involved in various biological processes. Up to now, the function of circRNAs in hepatocellular carcinoma (HCC) is still poorly known. qRT-PCR was used to test circ_0014717 expression in HCC tissue samples and cells was determined. It was shown that circ_0014717 was significantly decreased in HCC. Then, we observed overexpression of circ_0014717 obviously repressed HCC cell growth, migration and invasion. Next, we predicted circ_0014717 acted as a sponge of miR-668-3p. miR-668-3p has been reported to participate in several diseases. In our work, it was shown miR-668-3p was greatly increased in HCC and the direct binding sites between circ_0014717 and miR-668-3p were validated. In addition, B-cell translocation gene 2 (BTG2) is closely involved in cellular carcinogenic processes. BTG2 was predicted as a target for miR-668-3p. By performing rescue assays, we demonstrated that circ_0014717 repressed HCC progression via inhibiting BTG2 expression and sponging miR-668-3p. It was manifested loss of circ_0014717 induced HCC progression, which was reversed by BTG2 in Hep3B cells. In conclusion, our findings illustrated a novel circ_0014717/miR-668-3p/BTG2 regulatory signaling pathway in HCC.