Abstract
Helicobacter pylori infection is a major risk factor for the development of gastric cancer. Aberrant expression of microRNAs is strongly implicated in gastric tumorigenesis; however, their contribution in response to H. pylori infection has not been fully elucidated. In this study, we evaluated the expression ofmiR-135b-5p and its role in gastric cancer. We describe the overexpression of miR-135b-5p in human gastric cancer tissue samples compared with normal tissue samples. Furthermore, we found that miR-135b-5p is also up-regulated in gastric tumors from the trefoil factor 1-knockout mouse model. Infection with H. pylori induced the expression of miR-135b-5p in the in vitro and in vivo models. miR-135b-5p induction was mediated by NF-kB. Treatment of gastric cancer cellswith TNF-a inducedmiR-135b-5p in aNF-kB-dependentmanner.Mechanistically,we found thatmiR-135b-5p targets Kr üppel-like factor 4 (KLF4) and binds to its 39 UTR, leading to reduced KLF4 expression. Functionally, high levels of miR-135b-5p suppress apoptosis and induce cisplatin resistance. Our results uncovered a mechanistic link between H. pylori infection andmiR-135b-5p-KLF4, suggesting that targetingmiR-135b-5p could be a potential therapeutic approach to circumvent resistance to cisplatin.
Original language | English (US) |
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Pages (from-to) | 264-274 |
Number of pages | 11 |
Journal | FASEB Journal |
Volume | 33 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2019 |
Keywords
- H. pylori
- Inflammation
- KLF4
- MicroRNA
- Tff1 knockout
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics