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

8 Citations (Scopus)

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

Fingerprint

Helicobacter pylori
Cisplatin
Stomach Neoplasms
Helicobacter Infections
Tissue
Untranslated Regions
NF-kappa B
MicroRNAs
Tumors
Stomach
Apoptosis
Knockout Mice
Carcinogenesis
Infection
Neoplasms
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer. / Shao, Linlin; Chen, Zheng; Soutto, Mohammed; Zhu, Shoumin; Lu, Heng; Romero-Gallo, Judith; Peek, Richard; Zhang, Shutian; El-Rifai, Wael.

In: FASEB Journal, Vol. 33, No. 1, 01.01.2019, p. 264-274.

Research output: Contribution to journalArticle

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, vol. 33, no. 1, pp. 264-274. https://doi.org/10.1096/fj.201701456RR
Shao, Linlin ; Chen, Zheng ; Soutto, Mohammed ; Zhu, Shoumin ; Lu, Heng ; Romero-Gallo, Judith ; Peek, Richard ; Zhang, Shutian ; El-Rifai, Wael. / Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer. In: FASEB Journal. 2019 ; Vol. 33, No. 1. pp. 264-274.
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