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

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.

MiR-132 prohibits proliferation, invasion, migration, and metastasis in breast cancer by targeting HN1

“…Thus miR-NA may exhibit different expression levels between normal and cancer cells or tissues. For instance, miR-205 level is significantly lower in breast cancer cells and tissues than in normal breast and corresponding non-tumor breast tissues [18]; MiR-210 is down-regulated in Hp-infected gastric cancer [19]. Thus, downregulation of the microRNAs may be an important step in tumor progression.…”

Genetics and Molecular Pathogenesis of Gastric Adenocarcinoma

“…113 to stimulate cellular proliferation (e.g., mir-210). 123 Work is also ongoing to characterize the role of miRNAs in tumor progression and drug resistance, with numerous studies reporting miRNA expression patterns associated with patient outcome. 124,125 For example, miRNAs in the mir-200 family play a key role in regulating EMT via EMT regulators such as ZEB1, and mir-200 downregulaton is associated with poor prognosis.…”

The Effect of MicroRNA-375 Overexpression, an Inhibitor of Helicobacter pylori-Induced Carcinogenesis, on lncRNA SOX2OT

“…Recent studies have characterized deregulation of host miRNAs following infection with extracellular ( H. pylori ) (12), or intracellular ( Salmonella enterica ) (13), Gram-negative bacteria, as well as in the response to Gram-positive ( Listeria monocytogenes ) (14) and other pathogenic bacteria ( Mycobacterium (15) and Francisella species (16)).…”