Oncotarget

Research Papers:

Induction of SOCS3 by liver X receptor suppresses the proliferation of hepatocellular carcinoma cells

Haojun Xiong, Yan Zhang, Shan Chen, Zhenhong Ni, Jintao He, Xinzhe Li, Bo Li, Kai Zhao, Fan Yang, Yijun Zeng, Bingbo Chen and Fengtian He _

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Oncotarget. 2017; 8:64083-64094. https://doi.org/10.18632/oncotarget.19321

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Abstract

Haojun Xiong1, Yan Zhang1, Shan Chen1, Zhenhong Ni1, Jintao He2, Xinzhe Li1, Bo Li1, Kai Zhao1, Fan Yang1, Yijun Zeng1, Bingbo Chen3 and Fengtian He1

1Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China

2Battalion 17 of Students, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China

3Laboratory Animal Center, Third Military Medical University, Chongqing 400038, China

Correspondence to:

Fengtian He, email: [email protected]

Bingbo Chen, email: [email protected]

Keywords: HCC, LXR, SOCS3

Received: April 28, 2017     Accepted: June 10, 2017     Published: July 18, 2017

ABSTRACT

Liver X receptor (LXR), a member of nuclear receptor superfamily, is involved in the regulation of glucose, lipid and cholesterol metabolism. Recently, it has been reported that LXR suppress different kinds of cancers including hepatocellular carcinoma (HCC). However, the corresponding mechanism is still not well elucidated. In the present study, we found that activation of LXR downregulated cyclin D1 while upregulated p21 and p27 by elevating the level of suppressor of cytokine signaling 3 (SOCS3), leading to the cell cycle arrest at G1/S phase and growth inhibition of HCC cells. Moreover, we demonstrated that LXRα (not LXRβ) mediated the induction of SOCS3 in HCC cells. Subsequently, we showed that LXR activation enhanced the mRNA stability of SOCS3, but had no significant influence on the transcriptional activity of SOCS3 gene promoter. The experiments in nude mice revealed that LXR agonist inhibited the growth of xenograft tumors and enhanced SOCS3 expression in vivo. These results indicate that “LXRα-SOCS3-cyclin D1/p21/p27” is a novel pathway by which LXR exerts its anti-HCC effects, suggesting that the pathway may be a new potential therapeutic target for HCC treatment.


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