Epigenetic silencing of miR-338-3p contributes to tumorigenicity in gastric cancer by targeting SSX2IP

PLoS One. 2013 Jun 24;8(6):e66782. doi: 10.1371/journal.pone.0066782. Print 2013.

Abstract

MicroRNA has been recently recognized as playing a prominent role in tumorigenesis and metastasis. Here, we report that miR-338-3p was epigenetically silenced in gastric cancer, and its down-regulation was significantly correlated with gastric cancer clinicopathological features. Strikingly, restoring miR-338-3p expression in SGC-7901 gastric cancer cells inhibited proliferation, migration, invasion and tumorigenicity in vitro and in vivo, at least partly through inducing apoptosis. Furthermore, we demonstrate the oncogene SSX2IP is a target of miR-338-3p. We propose that miR-338-3p functions as a tumor suppressor in gastric cancer, and the methylation status of its CpG island could serve as a potential diagnostic marker for gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Epigenesis, Genetic / genetics*
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / therapy*
  • Xenograft Model Antitumor Assays

Substances

  • MIRN338 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • Repressor Proteins
  • synovial sarcoma X breakpoint proteins

Grants and funding

This study was supported by grants from National Natural Science Foundation of China (numbers 30872476, 81072012, 81172324, 91229106, 30900670 and 81272749), Science and Technology Commission of Shanghai Municipality (numbers 10jc1411100, 09DZ1950100, 09DZ2260200, 11jc1407602 and 101409042000), Shanghai Key Discipline (S30204), and Key Projects in the National Science & Technology Pillar Program of China (numbers 2008BA152B03 and 2011BA203191), China Postdoctoral Science Foundation (number 2011M500796). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of manuscript.