Tumor suppressive microRNA-193b promotes breast cancer progression via targeting DNAJC13 and RAB22A

Int J Clin Exp Pathol. 2014 Oct 15;7(11):7563-70. eCollection 2014.

Abstract

Breast cancer is still a leading cause of cancer deaths in women. Despite improvements in therapeutic approaches in local control, metastatic relapse is almost always incurable, underlining the importance to better understand the biological bases that contribute to disease progression. In this study, we demonstrated that miR-193b was significantly down-regulated in two primary human breast cancer cell lines (MDA-MB-231 and MCF-7). Reconstitution of miR-193b expression resulted in decreasing cell proliferation, clonogenicity, migration and invasion. By using in silico prediction algorithms approach for target identification, we identified DNAJC13 (HPS40) and RAB22A to be direct targets of miR-193b. Concordantly, Re-expression of miR-193b decreased DNAJC13 (HPS40) and RAB22A expression. Luciferase reporter assays confirmed the direct interaction of miR-193b with both DNAJC13 (HPS40) and RAB22A. Our findings have demonstrated that miR-193b as a novel tumor suppressor plays an important role in breast cancer progression, understanding the mechanisms could account for the aggressive behaviour of breast cancer.

Keywords: Breast cancer; microRNA; target identification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*

Substances

  • DNAJC13 protein, human
  • MIRN193 microRNA, human
  • MicroRNAs
  • Molecular Chaperones
  • RAB22A protein, human
  • rab GTP-Binding Proteins