Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer

Linlin Shao, Zheng Chen, Mohammed Soutto, Shoumin Zhu, Heng Lu, Judith Romero-Gallo, Richard Peek, Shutian Zhang, Wael El-Rifai

Research output: Contribution to journalArticle

13 Scopus citations

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 languageEnglish (US)
Pages (from-to)264-274
Number of pages11
JournalFASEB Journal
Volume33
Issue number1
DOIs
StatePublished - Jan 1 2019

Keywords

  • H. pylori
  • Inflammation
  • KLF4
  • MicroRNA
  • Tff1 knockout

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Shao, L., Chen, Z., Soutto, M., Zhu, S., Lu, H., Romero-Gallo, J., Peek, R., Zhang, S., & El-Rifai, W. (2019). Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer. FASEB Journal, 33(1), 264-274. https://doi.org/10.1096/fj.201701456RR