TY - JOUR
T1 - Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection
AU - Kiga, Kotaro
AU - Mimuro, Hitomi
AU - Suzuki, Masato
AU - Shinozaki-Ushiku, Aya
AU - Kobayashi, Taira
AU - Sanada, Takahito
AU - Kim, Minsoo
AU - Ogawa, Michinaga
AU - Iwasaki, Yuka W.
AU - Kayo, Hiroyuki
AU - Fukuda-Yuzawa, Yoko
AU - Yashiro, Masakazu
AU - Fukayama, Masashi
AU - Fukao, Taro
AU - Sasakawa, Chihiro
N1 - Funding Information:
We would like to thank Dr P.J. Nielsen and Dr A. Sood for critical reading, and Dr Teruo Kirikae and Dr Hiroki Iwai for critical comments of the manuscript. We would like to thank Dr Hideo Iba and Dr Takeshi Haraguchi for kindly providing gastric cell lines, and Dr Zhenzi Piao for technical support. This work was supported by a Grant-in-Aid for Specially promoted Research (23000012 (C.S.)), a Grant-in-Aid for Scientific Research (B) (26293095 (H.M.)), and Grant-in-Aid for Challenging Exploratory Research (25670209 (H.M.)) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) and Japan Society for the Promotion of Science (JSPS). Part of this work was supported by grants from the Waksman Foundation, the Ichiro Kanehara Foundation, the Astellas Foundation for Research on Metabolic Disorders, the Uehara Memorial Foundation (H.M.), the Takeda Science Foundation (H.M.) and Max-Planck Gesellschaft and DFG SFB 620 (T.F.). C.S. acknowledges support from Yakult-Honsha Co., Ltd. K.K. is supported by a Research Fellowship for Young Scientists (JSPS).
Publisher Copyright:
© 2014 Macmillan Publishers Limited. All rights reserved.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84910145153&partnerID=8YFLogxK
U2 - 10.1038/ncomms5497
DO - 10.1038/ncomms5497
M3 - Article
C2 - 25187177
AN - SCOPUS:84910145153
SN - 2041-1723
VL - 5
JO - Nature communications
JF - Nature communications
M1 - 4497
ER -
