miR-148a increases the sensitivity to cisplatin by targeting Rab14 in renal cancer cells

Int J Oncol. 2017 Mar;50(3):984-992. doi: 10.3892/ijo.2017.3851. Epub 2017 Jan 17.

Abstract

MicroRNA (miR) can exert various biological functions by targeting oncogenes or tumor suppressor genes in numerous human malignancies. Recent evidence has shown that miR-148a increases the drug sensitivity of various cancer cells. Herein, we show that ectopic expression of miR-148a induces apoptosis, reduces clonogenicity, and increases the sensitivity to TRAIL and cisplatin in renal cancer cells. The luciferase reporter assay showed that miR-148a negatively regulated ras-related protein 14 (Rab14) expression by binding to the miR-148a binding site in the 3' untranslated region (3'UTR) of Rab14. Rab14-specific siRNA-induced downregulation of Rab14 increases the sensitivity to cisplatin, while forced expression of Rab14 lacking 3'-UTR abrogated the pro-apoptotic function of miR-148a in renal cancer cells. These findings suggest that miR-148a acts as a tumor suppressor and holds great potential for renal cancer therapy by directly targeting Rab14.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / genetics*
  • Binding Sites / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm / genetics
  • Genes, Tumor Suppressor
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / genetics*
  • MicroRNAs / genetics*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Tumor Stem Cell Assay
  • rab GTP-Binding Proteins / biosynthesis
  • rab GTP-Binding Proteins / genetics*

Substances

  • 3' Untranslated Regions
  • Antineoplastic Agents
  • MIRN148 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Rab14 protein, human
  • rab GTP-Binding Proteins
  • Cisplatin