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Sunitinib is the most commonly used first-line therapy for the treatment of advanced renal cell carcinoma (RCC), but intrinsic and extrinsic resistance to targeted therapies dramatically compromise the benefit of clinical outcome. Dissecting the underlying mechanisms and discovering reliable predictive biomarkers are urgently needed in clinic. Here, we discovered miR-885-5p was notably decreased after sunitinib treatment and associated with poor disease progression in clear cell renal cell carcinoma (ccRCC). In vitro and in vivo studies identified miR-885-5p inhibition contributed to sunitinib resistance. Mechanistically, sunitinib treatment reduced GATA1 expression, which in turn reduced its binding to MIR885 promoter and resulted in miR-885-5p downregulation in transcriptional level. In addition, PLIN3 was confirmed to be directly targeted by miR-885-5p and its upregulation significantly increased lipid droplets formation to decrease sunitinib sensitivity. Therefore, GATA1/miR-885-5p/ PLIN3 pathway may serve as a potential therapeutic strategy and a biomarker for sunitinib treatment in ccRCC. [ABSTRACT FROM AUTHOR]

There is increasing evidence suggesting that dysregulation of some microRNAs (miRNAs) may contribute to tumor progression and metastasis and have been proposed to be key regulators of diverse biological processes such as transcriptional regulation, cell growth and tumorigenesis. Previous studies have shown that miR-137 is dysregulated in some malignancies, but its role in bladder cancer is still unknown. In our study, we find that miR-137 is up-regulated in human bladder cancer tissues and cell lines. Moreover, the higher level of miR-137 was associated with pM or pTNM stage in clinical bladder cancer patients. Enforced expression of miR-137 in bladder cancer cells significantly enhanced their proliferation, migration and invasion. Bioinformatics analysis identified the tumor suppressor gene PAQR3 as a potential miR-137 target gene. Further studies indicated that miR-137 suppressed the expression of PAQR3 by binding to its 3′-untranslated region. Silencing of PAQR3 by small interfering RNAs phenocopied the effects of miR-137 overexpression, whereas restoration of PAQR3 in bladder cancer cells bladder cancer cells overexpressing miR-137, partially reversed the suppressive effects of miR-137. These findings indicate that miR-137 could be a potential oncogene in bladder cancer. [ABSTRACT FROM AUTHOR]