Obesity-associated miR-27a upregulation promotes hepatocellular carcinoma metastasis through suppressing SFRP1
Received 18 January 2018
Accepted for publication 3 May 2018
Published 1 June 2018 Volume 2018:11 Pages 3281—3292
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 2
Editor who approved publication: Professor Jianmin Xu
Yang Chen,1 Fan Zhang,2 Yawei Zhao,2 Kan He,2 Xiao Zheng,2 Yue Pan,2 Dan Shao,2 Pei Shang,2 Yongsheng Yang,1 Dan Zhang,1 Yingjun Xie,1 Xiaoxiao Yao,1 Li Chen,2 Jing Li,2 Xuewen Zhang1
1Department of Hepatobiliary and Pancreas Surgery, The Second Hospital of Jilin University, Changchun 130041, China; 2Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun 130021, China
Background: Obesity was a recognized risk factor for the development and progression of hepatocellular carcinoma (HCC). However, the effects and mechanisms by which obesity promotes HCC metastasis remain poorly understood.
Materials and methods: We cultured adipocyte induced by preadipocyte 3T3-L1 in vitro and established HCC metastasis model in obesity mouse in vivo to mimic the tumor microenvironment in obese status. The mechanisms underlying obesity-associated miR-27a upregulation promoting HCC metastasis were investigated.
Results: In this study, we showed that miR-27a was upregulated in adipocytes, obese mouse model and clinical samples, and the increased miR-27a level promoted migration and invasion in HCC cells, increased the number of metastasis nodes in obese mouse model, and was associated with poor clinical outcomes. Overexpressed secreted frizzled-related protein 1 in HCC cells and tissues significantly alleviated the upregulation of β-catenin and matrix metalloproteinase-7 induced by high level of miR-27a. Meanwhile, the E-cadherin expression decreased and Vimentin expression increased, linking with high level of β-catenin in high-fat group.
Conclusion: Taken together, our results have elucidated the critical role of extracellular miR-27a as a pro-metastatic factor in HCC and revealed that obesity-associated miR-27a upregulation promoted HCC metastasis through activated Wnt/β-catenin signaling by suppressing secreted frizzled-related protein 1. Our findings shed light on the novel mechanism underlying HCC metastasis and provided miR-27a as a promising target for obese liver cancer therapy.
Keywords: obesity, miR-27a, SFRP1, β-catenin, hepatocellular carcinoma
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