Regulation of Oncogenic Targets by the Tumor-Suppressive miR-139 Duplex (miR-139-5p and miR-139-3p) in Renal Cell Carcinoma.
Reona OkadaYusuke GotoYasutaka YamadaMayuko KatoShunichi AsaiShogo MoriyaTomohiko IchikawaNaohiko SekiPublished in: Biomedicines (2020)
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.
Keyphrases
- renal cell carcinoma
- poor prognosis
- prognostic factors
- induced apoptosis
- long non coding rna
- cell cycle arrest
- epithelial mesenchymal transition
- genome wide
- cell proliferation
- signaling pathway
- binding protein
- gene expression
- newly diagnosed
- ejection fraction
- free survival
- squamous cell carcinoma
- chronic kidney disease
- genome wide identification
- cell death
- papillary thyroid
- high throughput
- pi k akt
- atomic force microscopy