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


ABSTRACT: We previously found that both the guide and passenger strands of the miR-139 duplex (miR-139-5p and miR-139-3p, respectively) were downregulated in cancer tissues. Analysis of TCGA datasets revealed that low expression of miR-139-5p (p < 0.0001) and miR-139-3p (p < 0.0001) was closely associated with 5-year survival rates of patients with renal cell carcinoma (RCC). Ectopic expression assays showed that miR-139-5p and miR-139-3p acted as tumor-suppressive miRNAs in RCC cells. Here, 19 and 22 genes were identified as putative targets of miR-139-5p and miR-139-3p in RCC cells, respectively. Among these genes, high expression of PLXDC1, TET3, PXN, ARHGEF19, ELK1, DCBLD1, IKBKB, and CSF1 significantly predicted shorter survival in RCC patients according to TCGA analyses (p < 0.05). Importantly, the expression levels of four of these genes, PXN, ARHGEF19, ELK1, and IKBKB, were independent prognostic factors for patient survival (p < 0.05). We focused on PXN (paxillin) and investigated its potential oncogenic role in RCC cells. PXN knockdown significantly inhibited cancer cell migration and invasion, possibly by regulating epithelial-mesenchymal transition. Involvement of the miR-139-3p 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.

SUBMITTER: Okada R 

PROVIDER: S-EPMC7764717 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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

Okada Reona R   Goto Yusuke Y   Yamada Yasutaka Y   Kato Mayuko M   Asai Shunichi S   Moriya Shogo S   Ichikawa Tomohiko T   Seki Naohiko N  

Biomedicines 20201212 12


We previously found that both the guide and passenger strands of the <i>miR-139</i> duplex (<i>miR-139-5p</i> and <i>miR-139-3p</i>, respectively) were downregulated in cancer tissues. Analysis of TCGA datasets revealed that low expression of <i>miR-139-5p</i> (<i>p</i> < 0.0001) and <i>miR-139-3p</i> (<i>p</i> < 0.0001) was closely associated with 5-year survival rates of patients with renal cell carcinoma (RCC). Ectopic expression assays showed that <i>miR-139-5p</i> and <i>miR-139-3p</i> acte  ...[more]

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