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Onco Targets Ther. 2018 Jun 1;11:3281-3292. doi: 10.2147/OTT.S162978. eCollection 2018.

Obesity-associated miR-27a upregulation promotes hepatocellular carcinoma metastasis through suppressing SFRP1.

Author information

1
Department of Hepatobiliary and Pancreas Surgery, The Second Hospital of Jilin University, Changchun 130041, China.
2
Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.

Abstract

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:

SFRP1; hepatocellular carcinoma; miR-27a; obesity; β-catenin

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