Induction of SOCS3 by liver X receptor suppresses the proliferation of hepatocellular carcinoma cells.
Induction of SOCS3 by liver X receptor suppresses the proliferation of hepatocellular carcinoma cells.
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肝脏X受体诱导SOCS3抑制肝癌细胞增殖
DOI：
10.18632/oncotarget.19321
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发表时间：
2017-09-08
期刊：
影响因子：
--
通讯作者：
He F
中科院分区：
文献类型：
--
作者：
Xiong H;Zhang Y;Chen S;Ni Z;He J;Li X;Li B;Zhao K;Yang F;Zeng Y;Chen B;He F
肝X受体(LXR)是核受体超家族成员之一，参与糖、脂和胆固醇代谢的调节。近年来，研究发现LXR可抑制包括肝细胞癌在内的多种肿瘤的发生。然而，其相应的机制仍未得到很好的阐明。在本研究中，我们发现LXR的激活通过上调细胞因子信号转导抑制因子3(SOCS3)的水平，下调了细胞周期蛋白D1的表达，上调了p21和p27的表达，导致细胞周期停滞在G1/S期，抑制了肝癌细胞的生长。此外，我们还证明了LXRα(而不是LXRβ)介导了SOCS3在肝癌细胞中的诱导。随后，我们发现LXR激活增强了SOCS3基因的mRNA稳定性，但对SOCS3基因启动子的转录活性没有显著影响。在裸鼠体内的实验表明，LXR激动剂抑制了移植瘤的生长，并增强了SOCS3的表达。这些结果表明，“LXRα-SOCS3-cyClind1/p21/p27”是LXR发挥抗肝癌作用的新途径，提示该途径可能成为治疗肝癌的新靶点。
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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影响因子：
29.4
作者：
El-Serag HB
通讯作者：
El-Serag HB
肿瘤 SOCS3 甲基化状态预测 HCC 患者对 TACE 的治疗反应和预后
影响因子：
--
作者：
Jiang BG;Wang N;Huang J;Yang Y;Sun LL;Pan ZY;Zhou WP
通讯作者：
Zhou WP
影响因子：
32.4
作者：
Ito, Ayaka;Hong, Cynthia;Oka, Kazuhiro;Salazar, Jon V.;Diehl, Cody;Witztum, Joseph L.;Diaz, Mercedes;Castrillo, Antonio;Bensinger, Steven J.;Chan, Lawrence;Tontonoz, Peter
通讯作者：
Tontonoz, Peter
影响因子：
--
作者：
Courtaut F;Derangère V;Chevriaux A;Ladoire S;Cotte AK;Arnould L;Boidot R;Rialland M;Ghiringhelli F;Rébé C
通讯作者：
Rébé C
影响因子：
4.4
作者：
Ehlting, Christian;Lai, Wi S.;Bode, Johannes G.
通讯作者：
Bode, Johannes G.