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  • Original Article
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MiR-22 sustains NLRP3 expression and attenuates H. pylori-induced gastric carcinogenesis

Oncogene volume 37, pages 884–896 (2018)Cite this article

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Abstract

Chronic inflammation is the primary cause of gastric cancer (GC). NLRP3, as an important inflammasome component, has crucial roles in initiating inflammation. However, the potential roles of NLRP3 in GC is unknown. Here, we show that NLRP3 expression is markedly upregulated in GC, which promotes NLRP3 inflammasome activation and interleukin-1β (IL-1β) secretion in macrophages. In addition, NLRP3 binds to cyclin-D1 (CCND1) promoter and promotes its transcription in gastric epithelial cells. Consequently, NLRP3 enhances epithelial cells proliferation and GC tumorigenesis. Furthermore, we identify miR-22, which is constitutively expressed in gastric mucosa, as a suppressor of NLRP3. MiR-22 directly targets NLRP3 and attenuates its oncogenic effects in vitro and in vivo. However, Helicobacter pylori (H. pylori) infection suppresses miR-22 expression, while enhances NLRP3 expression, and that triggers uncontrolled proliferation of epithelial cells and the emergence of GC. Thus, our research describes a mechanism by which miR-22 suppresses NLRP3 and maintains homeostasis of gastric microenvironments and suggests miR-22 as a potential target for the intervention of GC.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81772151, 81571960, 81371781, 81670146, 81470318, 81372680, 81471991 and 81501720), the Science Foundation of Shandong Province (2017GSF18194, 2017GSF18109, 2014GSF118114 and ZR2014HQ070), and the Independent Innovation Foundation of Shandong University.

Author contributions

JJ conceived of the study and provided overall direction; SL, WZ and JJ designed the experiments; SL, XL, LM, LS, TL, LZ, AS, WS and CC performed the experiments; SL, WZ and JJ analyzed the data and wrote the paper.

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Authors and Affiliations

  1. Department of Microbiology and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Shandong University, Jinan, Shandong, China

    S Li, X Liang, L Ma, L Shen, T Li, L Zheng, A Sun, W Shang & J Jia

  2. Cancer Center, Qilu Hospital, Shandong University, Jinan, Shandong, China

    C Chen

  3. Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Shandong University, Jinan, Shandong, China

    W Zhao

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Correspondence to W Zhao or J Jia.

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Li, S., Liang, X., Ma, L. et al. MiR-22 sustains NLRP3 expression and attenuates H. pylori-induced gastric carcinogenesis. Oncogene 37, 884–896 (2018). https://doi.org/10.1038/onc.2017.381

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