miR-203 downregulates Yes-1 and suppresses oncogenic activity in human oral cancer cells

J Biosci Bioeng. 2015 Oct;120(4):351-8. doi: 10.1016/j.jbiosc.2015.02.002. Epub 2015 Apr 21.

Abstract

The purpose of this study was to elucidate the molecular mechanisms of microRNA-203 (miR-203) as a tumor suppressor in KB human oral cancer cells. MicroRNA microarray results showed that the expression of miR-203 was significantly down-regulated in KB cells compared with normal human oral keratinocytes. The viability of KB cells was decreased by miR-203 in the time- and dose-dependent manners. In addition, over-expressed miR-203 not only increased the nuclear condensation but also significantly increased the apoptotic population of KB cells. These results indicated that the over-expression of miR-203 induced apoptosis of KB cells. Furthermore, the target gene array analyses revealed that the expression of Yes-1, a member of the Src family kinases (SFKs), was significantly down-regulated by miR-203 in KB cells. Moreover, both the mRNA and protein levels of Yes-1 were strongly reduced in KB cells transfected with miR-203. Therefore, these results indicated that Yes-1 is predicted to be a potential target gene of miR-203. Through a luciferase activity assay, miR-203 was confirmed to directly targets the Yes-1 3' untranslated region (UTR) to suppress gene expression. Therefore, our findings indicate that miR-203 induces the apoptosis of KB cells by directly targeting Yes-1, suggesting its application in anti-cancer therapeutics.

Keywords: Apoptosis; Oral cancer cells; Tumor suppressor; Yes-1; miR-203.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Apoptosis / genetics*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Down-Regulation*
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, Tumor Suppressor*
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / therapeutic use
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Proteins c-yes / biosynthesis
  • Proto-Oncogene Proteins c-yes / genetics*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Transfection

Substances

  • 3' Untranslated Regions
  • MIRN203 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Proto-Oncogene Proteins c-yes
  • YES1 protein, human