NF-kappaB-dependent MicroRNA-425 upregulation promotes gastric cancer cell growth by targeting PTEN upon IL-1β induction

Molecular Cancer

Research

Wen Zhang¹  Yue Fan¹  Lili Xu¹  Dingfang Cai¹  Xixi Gu¹  Jun Ma¹  Jun Liu¹  Zhiming Wang²  Jianjun Zhang³ 

[1] Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, PR China;Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, PR China;Department of Oral & Maxillofacial-Head Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China;

关键词: IL-1β;    NF-kappaB;    miR-425;    PTEN;    Gastric cancer;   

DOI  :  10.1186/1476-4598-13-40

 received in 2013-10-08, accepted in 2014-02-20,  发布年份 2014

来源: Springer

【 摘 要 】

Overexpression of the proinflammatory cytokine IL-1β is associated with diverse diseases, including cancer. Alteration of microRNAs has been observed in cancer cells exposed to proinflammatory cytokines, yet their function in inflammation stress remains elusive. Here, we show that IL-1β induces the upregulation of miR-425, which negatively regulates phosphatase and tensin homolog expression by targeting its 3’ UTR. An increase in miR-425 depends on IL-1β-induced NF-kappaB activation, which enhances miR-425 gene transcription upon IL-1β induction. Consequently, repression of phosphatase and tensin homolog by miR-425 promotes gastric cancer cell proliferation, which is required to protect cells from cisplatin-induced apoptosis. Taken together, our data support a critical role for NF-kappaB-dependent upregulation of miR-425, which represents a new pathway for the repression of phosphatase and tensin homolog activation and the promotion of cell survival upon IL-1β induction.

【 授权许可】

Unknown   
© Ma et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.