miR-200c inhibits breast cancer proliferation by targeting KRAS

Oncotarget. 2015 Oct 27;6(33):34968-78. doi: 10.18632/oncotarget.5198.


The microRNA, miR-200c, is involved in the tumorigenesis and progression of a variety of cancers. The purpose of this study was to investigate the expression, mechanism and prognostic roles of miR-200c in breast cancer. We found that miR-200c was downregulated in both breast cancer tissue and cell lines using quantitative real-time PCR (qRT-PCR). In situ hybridization (ISH) and microarrays showed that low miR-200c expression was associated with poor patient overall survival (OS) and disease free survival (DFS). We used luciferase reporter plasmids to find that miR-200c inhibited the AKT and ERK pathways by directly targeting KRAS. Repression of KRAS by miR-200c suppressed the proliferation and survival of breast cancer cells in vitro and in vivo. miR-200c also had an anti-tumor effect by negatively regulating KRAS in a xenograft mouse model. Our findings provide clues regarding the role of miR-200c as a tumor suppressor in breast cancer through the inhibition of KRAS translation both in vitro and in vivo. miR-200c could be a potential therapeutic target in breast cancer.

Keywords: KRAS; breast cancer; miR-200c; microRNA; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Cell Proliferation / genetics
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Genes, Tumor Suppressor / physiology*
  • Humans
  • In Situ Hybridization
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Proteins p21(ras) / biosynthesis*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Real-Time Polymerase Chain Reaction
  • Transfection
  • Xenograft Model Antitumor Assays


  • KRAS protein, human
  • MIRN200 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins p21(ras)