Oncotarget

Research Papers:

Chronic inflammation contributes to the development of hepatocellular carcinoma by decreasing miR-122 levels

Changfei Li, Mengmeng Deng, Jun Hu, Xin Li, Lizhao Chen, Ying Ju, Junli Hao and Songdong Meng _

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Oncotarget. 2016; 7:17021-17034. https://doi.org/10.18632/oncotarget.7740

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Abstract

Changfei Li1, Mengmeng Deng1, Jun Hu1, Xin Li1, Lizhao Chen1, Ying Ju1, Junli Hao2, Songdong Meng1

1CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China

2School of Biomedical Sciences, Chengdu Medical college, Chengdu, China

Correspondence to:

Songdong Meng, e-mail: mengsd@im.ac.cn

Junli Hao, e-mail: haojunli00@163.com

Keywords: C/EBPα, miR-122, IL-6, c-myc, TNF-α

Received: October 19, 2015    Accepted: February 05, 2016    Published: February 26, 2016

ABSTRACT

Persistent inflammation in chronic hepatitis plays a major role in the development of hepatocellular carcinoma (HCC). In this study, the major inflammatory cytokines expressed in chronic hepatitis, IL-6 and TNF-α, induced a marked decrease in microRNA-122 (miR-122) levels, and miR-122 expression was downregulated in the livers of chronic hepatitis B (CHB) patients. The decrease of miR-122 caused upregulation of the proinflammatory chemokine CCL2. IL-6 and TNF-α suppressed miR-122 both by directly downregulating the transcription factor C/EBPα and indirectly upregulating c-myc, which blocks C/EBPα-mediated miR-122 transcription. In addition, IL-6 and TNF-α levels were elevated and miR-122 levels were decreased in mouse and rat models of diethylnitrosamine (DEN)-induced HCC. Restoration of miR-122 levels through delivery of agomir-122 suppressed DEN-induced hepatocarcinogenesis in mice. Our results show that inflammation-induced miR-122 downregulation in hepatitis contributes to carcinogenesis and suggest that increasing miR-122 may be an effective strategy for preventing HCC development in CHB patients.


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