MicroRNA-145 functions as a tumor suppressor by targeting matrix metalloproteinase 11 and Rab GTPase family 27a in triple-negative breast cancer

Cancer Gene Ther. 2016 Aug;23(8):258-65. doi: 10.1038/cgt.2016.27. Epub 2016 Jul 1.

Abstract

Although increasing evidence has documented that microRNA-145 (miR-145) acts as a tumor suppressor in breast cancer, its exact role in triple-negative breast cancer (TNBC) remains poorly defined. In this study, the expression of miR-145 in human TNBC cells and samples from 30 patients was analyzed by stem-loop real-time PCR. We found that miR-145 was significantly downregulated in TNBC tissues and cells. Upregulating miR-145 in HCC1937 cells dramatically suppressed cell proliferation and induced G1-phase arrest, whereas MDA-MB-231 cells did not show growth inhibition. MiR-145 exhibited an inhibitory role in cell invasion through the post-transcriptional regulation of the novel targets MMP11 and Rab27a in TNBC cells. Additionally, miR-145 silencing could be reversed by 5-aza-2'-deoxycytidine (DAC). These results demonstrated that miR-145 has an inhibitory role in TNBC malignancy by targeting MMP11 and Rab27a, which might be potential therapeutic and diagnostic targets for TNBC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DNA Methylation
  • Down-Regulation
  • Ectopic Gene Expression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor*
  • Humans
  • Matrix Metalloproteinase 11 / genetics*
  • Matrix Metalloproteinase 11 / metabolism
  • MicroRNAs / genetics*
  • Promoter Regions, Genetic
  • RNA Interference*
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / metabolism
  • rab27 GTP-Binding Proteins / genetics*
  • rab27 GTP-Binding Proteins / metabolism

Substances

  • MIRN145 microRNA, human
  • MicroRNAs
  • rab27 GTP-Binding Proteins
  • Matrix Metalloproteinase 11
  • RAB27A protein, human