miR-106a is frequently upregulated in gastric cancer and inhibits the extrinsic apoptotic pathway by targeting FAS

Mol Carcinog. 2013 Aug;52(8):634-46. doi: 10.1002/mc.21899. Epub 2012 Mar 16.

Abstract

Emerging evidence has shown the association of aberrantly expressed miR-106a with cancer development, however, little is known about its potential role in gastric carcinogenesis. In our present study, obviously overexpressed miR-106a was found in gastric cancer tissues compared with their nontumor counterparts. Suppression of miR-106a significantly inhibited gastric cancer cell proliferation and triggered apoptosis. Bioinformatic analysis combining with validation experiments identified FAS as a direct target of miR-106a. Rescue experiments and examination of caspase-8, PARP and caspase-3 further approved that miR-106a could inhibit gastric cancer cell apoptosis through interfering with FAS-mediated apoptotic pathway. Moreover, a significant inverse correlation was found between miR-106a and FAS expression not only in gastric cancer cell lines but also in gastric cancer specimens. Taken together, these findings suggest that ectopicly overexpressed miR-106a may play an oncogenic role in gastric carcinogenesis and impair extrinsic apoptotic pathway through targeting FAS.

Keywords: FAS; apoptosis; gastric cancer; miR-106a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Apoptosis / genetics*
  • Base Pairing
  • Base Sequence
  • Cell Death / genetics
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Staging
  • Sequence Alignment
  • Signal Transduction*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • fas Receptor / genetics*
  • fas Receptor / metabolism

Substances

  • 3' Untranslated Regions
  • MIRN106 microRNA, human
  • MicroRNAs
  • fas Receptor