Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection

Kotaro Kiga, Hitomi Mimuro, Masato Suzuki, Aya Shinozaki-Ushiku, Taira Kobayashi, Takahito Sanada, Minsoo Kim, Michinaga Ogawa, Yuka W. Iwasaki, Hiroyuki Kayo, Yoko Fukuda-Yuzawa, Masakazu Yashiro, Masashi Fukayama, Taro Fukao, Chihiro Sasakawa

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78 Citations (Scopus)

Abstract

Persistent colonization of the gastric mucosa by Helicobacter pylori (Hp) elicits chronic inflammation and aberrant epithelial cell proliferation, which increases the risk of gastric cancer. Here we examine the ability of microRNAs to modulate gastric cell proliferation in response to persistent Hp infection and find that epigenetic silencing of miR-210 plays a key role in gastric disease progression. Importantly, DNA methylation of the miR-210 gene is increased in Hp-positive human gastric biopsies as compared with Hp-negative controls. Moreover, silencing of miR-210 in gastric epithelial cells promotes proliferation. We identify STMN1 and DIMT1 as miR-210 target genes and demonstrate that inhibition of miR-210 expression augments cell proliferation by activating STMN1 and DIMT1. Together, our results highlight inflammation-induced epigenetic silencing of miR-210 as a mechanism of induction of chronic gastric diseases, including cancer, during Hp infection.

Original languageEnglish
Article number4497
JournalNature communications
Volume5
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Kiga, K., Mimuro, H., Suzuki, M., Shinozaki-Ushiku, A., Kobayashi, T., Sanada, T., Kim, M., Ogawa, M., Iwasaki, Y. W., Kayo, H., Fukuda-Yuzawa, Y., Yashiro, M., Fukayama, M., Fukao, T., & Sasakawa, C. (2014). Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection. Nature communications, 5, [4497]. https://doi.org/10.1038/ncomms5497