Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, 12525Army Medical University (Third Military Medical University), Chongqing, China.
Department of Hepatobiliary Surgery, Daping Hospital (Army Medical Center), 12525Army Medical University (Third Military Medical University), Chongqing, China.
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820967473. doi: 10.1177/1533033820967473.
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. 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.
miR-124-3p 通过调控其靶基因被鉴定为肝癌（HCC）中的一种新型肿瘤抑制因子和潜在治疗靶点。然而，miR-124-3p 在 HCC 中的上游调控机制尚未完全阐明。转录因子肝 X 受体（LXR）在抑制 HCC 细胞增殖中发挥着关键作用，但尚不清楚 LXR 是否参与 miR-124-3p 的调控。在本研究中，我们证明了 miR-124-3p 的表达与 HCC 中的 LXR 呈正相关，LXR 激动剂显著抑制 HCC 细胞的生长。此外，激动剂激活 LXR 可上调 miR-124-3p 的表达，并下调其靶基因 cyclin D1 和 cyclin-dependent kinase 6 (CDK6) 的表达。机制上，miR-124-3p 介导了 LXR 诱导的 HCC 细胞生长抑制和 cyclin D1 和 CDK6 表达下调。实验还证实，LXR 诱导的 miR-124-3p 表达抑制 HCC 异种移植瘤的生长以及 cyclin D1 和 CDK6 的表达。我们的研究结果表明，miR-124-3p 是 LXR 的一个新的靶基因，LXR 通过调控 miR-124-3p-cyclin D1/CDK6 通路在 HCC 细胞增殖中发挥着关键作用。LXR-miR-124-3p-cyclin D1/CDK6 通路可能是 HCC 治疗的一个新的潜在治疗靶点。
