MiR-429 regulates rat liver regeneration and hepatocyte proliferation by targeting JUN/MYC/BCL2/CCND1 signaling pathway
MiR-429 regulates rat liver regeneration and hepatocyte proliferation by targeting JUN/MYC/BCL2/CCND1 signaling pathway
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MiR-429通过靶向JUN/MYC/BCL2/CCND1信号通路调控大鼠肝再生和肝细胞增殖
DOI：
10.1016/j.cellsig.2018.06.013
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Cunshuan Xu
中科院分区：
文献类型：
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作者：
Chunyan Zhang;Cuifang Chang;Hang Gao;Qiwen Wang;Fuchun Zhang;Cunshuan Xu
越来越多的证据表明miR-429参与多种人类癌症的肿瘤抑制。然而，其在肝再生中的作用仍未被探索。肝脏再生是一个高度协调的过程，可以通过microRNA（miRNAs）进行调节，尽管其机制在很大程度上尚不清楚。在这项研究中，我们旨在确定miR-429在肝再生过程中肝细胞增殖中的作用。首先，我们进行了微阵列分析和qRT-PCR。结果表明，大鼠肝部分切除后30 h，肝组织中miR-429水平显著降低，miR-429过表达可干扰肝细胞BRL-3A增殖和G1期向S期的转换，促进肝细胞凋亡。相比之下，miR-429下调具有相反的作用。MiR-429在体外和体内负调节JUN表达。在使用JUN siRNA后，我们发现JUN抑制介导miR-429在肝细胞增殖和生长中的作用，并且miR-429负调节JUN/MYC/BCL 2/CCND 1信号通路。我们的研究结果还表明，miR-429通过靶向JUN/MYC/BCL 2/CCND 1抑制肝细胞增殖和肝再生。
Increasing evidence indicates that miR-429 is involved in tumor suppression in various human cancers. However, its role in liver regeneration remains unexplored. Liver regeneration is a highly orchestrated process that can be regulated by microRNAs (miRNAs), although the mechanisms are largely unclear. In this study, we aimed to identify the role of miR-429 in hepatocyte proliferation during liver regeneration. First, we performed microarray analysis and qRT-PCR. Results indicated that miR-429 level in rat liver markedly decreased 30 h after partial hepatectomy, and miR-429 overexpression disrupted BRL-3A proliferation and the transition of G1 to S phase in rat hepatocyte and promoted hepatocyte apoptosis. By contrast, miR-429 down-regulation had inverse effects. MiR-429 negatively regulated JUN expression in vitro and in vivo. After using JUN siRNA, we found that JUN inhibition mediates the effect of miR-429 in hepatocyte proliferation and growth and miR-429 negatively regulates JUN/MYC/BCL2/CCND1 signaling pathways. Our results also indicated that miR-429 inhibits hepatocyte proliferation and liver regeneration by targeting JUN/MYC/BCL2/CCND1.