Upregulation of miR-124-3p by Liver X Receptor Inhibits the Growth of Hepatocellular Carcinoma Cells Via Suppressing Cyclin D1 and CDK6.
Upregulation of miR-124-3p by Liver X Receptor Inhibits the Growth of Hepatocellular Carcinoma Cells Via Suppressing Cyclin D1 and CDK6.
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肝脏 X 受体上调 miR-124-3p 通过抑制细胞周期蛋白 D1 和 CDK6 抑制肝细胞癌细胞的生长
DOI：
10.1177/1533033820967473
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发表时间：
2020-01
影响因子：
2.8
通讯作者：
Huang G
中科院分区：
文献类型：
--
作者：
Zhong D;Lyu X;Fu X;Xie P;Liu M;He F;Huang G
MiR-124- 3 p是一种新型的肿瘤抑制因子，通过调控靶基因的表达而成为肝细胞癌（HCC）治疗的潜在靶点。然而，mir-124- 3 p在HCC中的上游调控机制尚未完全了解。转录因子肝X受体（liver X receptor，LXR）在抑制肝癌细胞增殖中起关键作用，但LXR是否参与mir-124- 3 p的调控尚不清楚。在本研究中，我们证明了肝癌中mir-124- 3 p的表达与LXR的表达呈正相关，并且LXR激动剂显著抑制肝癌细胞的生长。此外，用激动剂激活LXR上调mir-124- 3 p的表达，并反过来下调细胞周期蛋白D1和细胞周期蛋白依赖性激酶6（CDK 6）的表达，这是mir-124- 3 p的靶基因。在机制上，miR-124- 3 p介导LXR诱导的HCC细胞生长抑制以及细胞周期蛋白D1和CDK 6表达下调。体内实验也证实，LXR诱导的miR-124- 3 p表达抑制HCC异种移植肿瘤的生长，以及细胞周期蛋白D1和CDK 6的表达。我们的研究结果表明，miR-124- 3 p是LXR的一个新的靶基因，LXR对miR-124- 3 p-cyclin D1/CDK 6通路的调控在HCC细胞增殖中起着至关重要的作用。LXR-miR-124- 3 p-cyclin D1/CDK 6通路可能成为肝癌治疗的新靶点。
MiR-124-3p has been identified as a novel tumor suppressor and a potential therapeutic target in hepatocellular carcinoma (HCC) through regulating its target genes. However, the upstream regulatory mechanisms of mir-124-3p in HCC has not been fully understood. The transcription factor liver X receptor (LXR) plays a critical role in suppressing the proliferation of HCC cells, but it is unclear whether LXR is involved in the regulation of mir-124-3p. In the present study, we demonstrated that the expression of mir-124-3p was positively correlated with that of LXR in HCC, and the cell growth of HCC was significantly inhibited by LXR agonists. Moreover, activation of LXR with the agonists up-regulated the expression of mir-124-3p, and in turn down-regulated cyclin D1 and cyclin-dependent kinase 6 (CDK6) expression, which are the target genes of mir-124-3p. Mechanistically, miR-124-3p mediates LXR induced inhibition of HCC cell growth and down-regulation of cyclin D1 and CDK6 expression. In vivo experiments also confirmed that LXR induced miR-124-3p expression inhibited the growth of HCC xenograft tumors, as well as cyclin D1 and CDK6 expression. Our findings revealed that miR-124-3p is a novel target gene of LXR, and regulation of the miR-124-3p-cyclin D1/CDK6 pathway by LXR plays a crucial role in the proliferation of HCC cells. LXR-miR-124-3p-cyclin D1/CDK6 pathway may be a novel potential therapeutic target for HCC treatment.
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影响因子：
11.2
作者：
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通讯作者：
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