MicroRNA‑99b promotes Helicobacter pylori‑induced autophagyand suppresses carcinogenesis by targeting mTOR

Yang,Liu; Li,Cong; Jia,Yujie

doi:10.3892/ol.2018.9269

MicroRNA‑99b promotes Helicobacter pylori‑induced autophagyand suppresses carcinogenesis by targeting mTOR

Authors:
- Liu Yang
- Cong Li
- Yujie Jia
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Affiliations: Department of Pathophysiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
Published online on: August 6, 2018 https://doi.org/10.3892/ol.2018.9269
Pages: 5355-5360

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Abstract

The regulatory mechanism of Helicobacter pylori‑induced gastric carcinogenesis remains unclear. Autophagy has previously been identified as an effective method of regulating carcinogenesis. In the present study, microRNA (miR)‑99b levels increased in H. pylori‑infected gastric cancer tissues and the BGC‑823 gastric cancer cell line. Overexpression of miR‑99b significantly enhanced autophagy, decreased intracellular bacterial loads and blocked cell proliferation. The effect on autophagy was demonstrated to be triggered by mammalian target of rapamycin inhibition. These results indicate that miR‑99b expression serves a key role in preventing H. pylori‑associated gastric cancer formation and this may provide potential targets for the future treatment of H. pylori‑associated diseases.

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1	Lee YC, Chiang TH, Chou CK, Tu YK, Liao WC, Wu MS and Graham DY: Association between Helicobacter pylori eradication and gastric cancer incidence: A systematic review and meta-analysis. Gastroenterology. 150:1113–1124. 2016. View Article : Google Scholar : PubMed/NCBI
2	Wessler S, Krisch LM, Elmer DP and Aberger F: From inflammation to gastric cancer-the importance of Hedgehog/GLI signaling in Helicobacter pylori-induced chronic inflammatory and neoplastic diseases. Cell Commun Signal. 15:152017. View Article : Google Scholar : PubMed/NCBI
3	Adamsson J, Lundin SB, Hansson LE, Sjovall H and Svennerholm AM: Immune responses against Helicobacter pylori in gastric cancer patients and in risk groups for gastric cancer. Helicobacter. 18:73–82. 2013. View Article : Google Scholar : PubMed/NCBI
4	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
5	Zhang Z, Li Z, Gao C, Chen P, Chen J, Liu W, Xiao S and Lu H: MiR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Lab Invest. 88:1358–1366. 2008. View Article : Google Scholar : PubMed/NCBI
6	Miao L, Liu K, Xie M, Xing Y and Xi T: miR-375 inhibits Helicobacter pylori-induced gastric carcinogenesis by blocking JAK2-STAT3 signaling. Cancer Immunol Immunother. 63:699–711. 2014. View Article : Google Scholar : PubMed/NCBI
7	Fulda S: Autophagy in cancer therapy. Front Oncol. 7:1282017. View Article : Google Scholar : PubMed/NCBI
8	Yang JC and Chien CT: A new approach for the prevention and treatment of Helicobacter pylori infection via upregulation of autophagy and downregulation of apoptosis. Autophagy. 5:413–414. 2009. View Article : Google Scholar : PubMed/NCBI
9	Zhan Z, Li Q, Wu P, Ye Y, Tseng HY, Zhang L and Zhang XD: Autophagy-mediated hmgb1 release antagonizes apoptosis of gastric cancer cells induced by vincristine via transcriptional regulation of mcl-1. Autophagy. 8:109–121. 2012. View Article : Google Scholar : PubMed/NCBI
10	Kim YC and Guan KL: mTOR: A pharmacologic target for autophagy regulation. J Clin Invest. 125:25–32. 2015. View Article : Google Scholar : PubMed/NCBI
11	Wu K, Yang L, Li C, Zhu CH, Wang X, Yao Y and Jia YJ: MicroRNA-146a enhance Helicobacter pylori induced cell apoptosis in human gastric cancer epithelial cell. Asian Pac J Cancer Prev. 15:5583–5586. 2014. View Article : Google Scholar : PubMed/NCBI
12	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCt method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
13	Wang D, Zhu X, Cui C, Dong M, Jiang H, Li Z, Liu Z, Zhu W and Wang JG: Discovery of novel acetohydroxyacid synthase inhibitors as active agents against Mycobacterium tuberculosis by virtual screening and bioassay. J Chem Inf Model. 53:343–353. 2013. View Article : Google Scholar : PubMed/NCBI
14	Li N, Tang B, Zhu ED, Li BS, Zhuang Y, Yu S, Lu DS, Zou QM, Xiao B and Mao XH: Increased mir-222 in H. pylori-associated gastric cancer correlated with tumor progression by promoting cancer cell proliferation and targeting reck. FEBS Lett. 586:722–728. 2012. View Article : Google Scholar : PubMed/NCBI
15	Ma L, Chen Y, Zhang B and Liu G: Increased microRNA-223 in Helicobacter pylori-associated gastric cancer contributed to cancer cell proliferation and migration. Biosci Biotechnol Biochem. 78:602–608. 2014. View Article : Google Scholar : PubMed/NCBI
16	Chang H, Kim N, Park JH, Nam RH, Choi YJ, Lee HS, Yoon H, Shin CM, Park YS, Kim JM, et al: Different MicroRNA expression levels in gastric cancer depending on Helicobacter pylori infection. Gut Liver. 9:188–196. 2014. View Article : Google Scholar
17	Chen D, Chen Z, Jin Y, Dragas D, Zhang L, Adjei BS, Wang A, Dai Y and Zhou X: MicroRNA-99 family members suppress homeobox a1 expression in epithelial cells. PLoS One. 8:e806252013. View Article : Google Scholar : PubMed/NCBI
18	Francipane MG and Lagasse E: mTOR pathway in colorectal cancer: An update. Oncotarget. 5:49–66. 2014. View Article : Google Scholar : PubMed/NCBI
19	Thiem S, Pierce TP, Palmieri M, Putoczki TL, Buchert M, Preaudet A, Farid RO, Love C, Catimel B, Lei Z, et al: mTORC1 inhibition restricts inflammation-associated gastrointestinal tumorigenesis in mice. J Clin Invest. 123:767–781. 2013.PubMed/NCBI
20	Greenfield LK and Jones NL: Modulation of autophagy by Helicobacter pylori and its role in gastric carcinogenesis. Trends Microbiol. 21:602–612. 2013. View Article : Google Scholar : PubMed/NCBI