MicroRNAs are short non-coding RNAs, which have been implicated in several biological processes. Aberrant expression of the microRNA miR-122 has frequently been reported in malignant cancers. However, the mechanism underlying the effects of miR-122 in renal cell carcinoma remains unknown. The aim of this study was to determine the biological function of miR-122 in renal cell carcinoma and to identify a novel molecular target regulated by miR-122. We measured the expression levels of Sprouty2 in six renal cell carcinoma tissue samples and adjacent non-tumor tissues by western blot analysis. We then used reverse transcription polymerase chain reaction to measure miR-122 levels in 40 primary renal cell carcinoma and adjacent non-malignant tissue samples. The effects of miR-122 down-regulation or Sprouty2 knockdown were evaluated via Cell Counting Kit-8 assay, flow cytometry, and western blot analysis. The relationship between miR-122 and Sprouty2 was determined using dual-luciferase reporter assays. Sprouty2 was down-regulated in renal cell carcinoma tissue samples compared with adjacent normal tissue. In contrast, miR-122 was up-regulated in primary renal cell carcinoma tissue samples compared with adjacent normal tissue samples. Down-regulation of miR-122 substantially weakened the proliferative ability of renal cell carcinoma cell lines in vitro. In contrast, Sprouty2 knockdown promoted the in vitro proliferation of renal cell carcinoma cell lines. The spry2 gene could therefore be a direct target of miR-122. In conclusion, miR-122 could act as a tumor promoter and potentially target Sprouty2. MiR-122 promotes renal cell carcinoma cell proliferation, migration, and invasion and could be a molecular target in novel therapies for renal cell carcinoma.
Purpose: To explore the effects of hypoxic non-small-cell lung cancer (NSCLC)-derived exosomes on NSCLC resistance to cisplatin. Materials and methods: Exosomes were isolated by differential centrifugation and characterized by transmission electron microscope and Western blotting. Quantitative real-time PCR was used to measure miR-21 levels. MTT assays and colony formation assays were performed to investigate the effects of hypoxia-induced exosomes on cisplatin resistance. Results: Hypoxic NSCLC cell-derived exosomes facilitate normoxic cell resistance to cisplatin. In addition, hypoxia enhanced the miR-21 expression in NSCLC cells and cell-derived exosomes. Interestingly, changes in miR-21 levels in the hypoxia-induced exosomes affected the sensitivity of recipient cells to cisplatin. Mechanically, exosomal miR-21 promoted cisplatin resistance by downregulating phosphatase and tensin homolog (PTEN). The expression of miR-21 in tumor cell lines and clinical NSCLC tumor samples was positively correlated with hypoxia-inducible factor-1α and negatively correlated with PTEN. Moreover, high miR-21 expression was associated with shorter median survival period in patients undergoing pharmacotherapy, but no association was observed in patients who were not under pharmacotherapy. Conclusion: Exosomal miR-21 derived from hypoxic NSCLC cells may promote cisplatin resistance, which indicates that exosomal miR-21 might be a potential biomarker and therapeutic target to address NSCLC chemoresistance. Keywords: non-small-cell lung cancer, exosomes, miR-21, cisplatin resistance, PTEN
BACKGROUND:The related mechanisms involved in allograft interstitial fibrosis and chronic allograft dysfunction (CAD), following renal transplant, remain largely unknown. Here, we explored the role of hepatocyte growth factor (HGF) treatment on the endothelial-to-mesenchymal transition (EndMT) as a new way to target and prevent kidney fibrosis and improve outcomes for renal transplant recipients. MATERIAL AND METHODS:We extracted proteins and mRNAs from human umbilical vein endothelial cells (HUVECs) and human renal glomerular endothelial cells (HRGECs) treated with transforming growth factor-beta1 (TGF-β1) and/or varying doses of HGF, and assessed the effect of HGF on the EndMT using western blotting, qRT-PCR, and ELISA assays. We utilized cell motility and migration assays to evaluate cell movement, and applied western blotting to assess the mechanism by which TGF-β1 induced the EndMT. RESULTS:HGF significantly attenuated the development of TGF-β1-induced EndMT in a concentration-dependent way, and weakened the abilities of motility and migration of both HUVECs and HRGECs. Moreover, our results reveal that the antifibrotic effect of HGF on the EndMT was associated with the TGF-β/Smad and Akt/mTOR/p70S6K signaling pathways. CONCLUSIONS:Our study suggests that HGF treatment significantly attenuates the development of EndMT induced by TGF-β1 via the TGFb/Smad and Akt/mTOR/P70S6K signaling, which provides novel insights into the prevention and treatment of interstitial fibrosis and CAD following renal transplant.
di-N-butylphthalate (DBP) is a ubiquitous environmental pollutant used for plastic coating and in the cosmetics industry. It has toxic effects on body health, especially the male reproductive system. Here, we investigated the effects of DBP on the male reproductive system of pubertal mice and explored the protective role of sulforaphane (SFN). The results showed that DBP significantly reduced the anogenital distance, testicular weight, sperm count and motility, and plasma and testicular testosterone levels and significantly increased the oxidative stress, sperm abnormalities, and testicular cell apoptosis. SFN supplementation ameliorated these effects. After DBP stimulation, the transcription factor nuclear factor erythroid-related factor 2 (Nrf2) was adaptively increased together with its target genes, such as HO-1 and NQO1. Upregulation of Nrf2 by SFN reduced the DBP-mediated intracellular oxidative toxicity and also increased testosterone secretion and spermatogenesis, which were decreased by DBP. These findings indicate that SFN can attenuate DBP-induced reproductive damage in pubertal mice via Nrf2-associated pathways.
Previous studies had researched the relationship between rs9642880 gene polymorphism and bladder cancer risk, but the results remained unclear. The comprehensive meta-analysis was performed to clarify this possible association. Relevant articles were searched from Pubmed, Embase and web of science. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to assess the strength of the association. The assessment of publication bias was conducted by Begg's funnel plots and Egger's regression test. A total of 7 casecontrol studies involving 4072 cases and 4898 controls were included in our study. Overall, an obvious relationship between rs9642880 polymorphism and increased risk of bladder cancer were detected in all models. Besides, the positive results were observed among both Caucasians and Asians when stratified by ethnicity. Moreover, when stratified by genotyping method, the significant results were detected in all genotyping methods except Sequenom. In addition, in the subgroup analysis by source of control, significant results were detected in both population and hospital based controls. This present meta-analysis with accurate and reliable results indicated that the T allele of SNP rs9642880 confers susceptibility to bladder cancer in both Asian and Caucasian populations.
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