Regulation of Oncogenic Targets by the Tumor-Suppressive miR-139 Duplex ( miR-139-5p and miR-139-3p ) in Renal Cell Carcinoma

We previously found that both the guide and passenger strands of the duplex ( and , respectively) were downregulated in cancer tissues. Analysis of TCGA datasets revealed that low expression of ( < 0.0001) and ( < 0.0001) was closely associated with 5-year survival rates of patients with renal cell carcinoma (RCC). Ectopic expression assays showed that and acted as tumor-suppressive miRNAs in RCC cells. Here, 19 and 22 genes were identified as putative targets of and in RCC cells, respectively. Among these genes, high expression of , , , , , , , and significantly predicted shorter survival in RCC patients according to TCGA analyses ( < 0.05). Importantly, the expression levels of four of these genes, , , , and , were independent prognostic factors for patient survival ( < 0.05). We focused on (paxillin) and investigated its potential oncogenic role in RCC cells. knockdown significantly inhibited cancer cell migration and invasion, possibly by regulating epithelial-mesenchymal transition. Involvement of the passenger strand in RCC molecular pathogenesis is a new concept. Analyses of tumor-suppressive-miRNA-mediated molecular networks provide important insights into the molecular pathogenesis of RCC.