Journal
FASEB JOURNAL
Volume 33, Issue 1, Pages 264-274Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201701456RR
Keywords
microRNA; tff1 knockout; inflammation; KLF4; H; pylori
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Funding
- U.S. National Institutes of Health, National Cancer Institute [R01CA93999, R01CA177372]
- U.S. Department of Veterans Affairs [1IK6BX003787, I01BX001179]
- Biostatistics and Bioinformatics Shared Resource at the Sylvester Comprehensive Cancer Center, University of Miami
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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 of miR-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-B. Treatment of gastric cancer cells with TNF- induced miR-135b-5p in a NF-B-dependent manner. Mechanistically, we found that miR-135b-5p targets Kruppel-like factor 4 (KLF4) and binds to its 3 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 and miR-135b-5p-KLF4, suggesting that targeting miR-135b-5p could be a potential therapeutic approach to circumvent resistance to cisplatin.Shao, L., Chen, Z., Soutto, M., Zhu, S., Lu, H., Romero-Gallo, J., Peek, R., Zhang, S., El-Rifai, W. Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer.
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