Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, 830046, China; State Key Laboratory Cultivation Base for Cell Differentiation Regulation and Henan Engineering Laboratory for Bioengineering and Drug Development, College of Life Science, Henan Normal University, Xinxiang 453007, Henan, China.
State Key Laboratory Cultivation Base for Cell Differentiation Regulation and Henan Engineering Laboratory for Bioengineering and Drug Development, College of Life Science, Henan Normal University, Xinxiang 453007, Henan, China.
Cell Signal. 2018 Oct;50:80-89. doi: 10.1016/j.cellsig.2018.06.013. Epub 2018 Jun 26.
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.
越来越多的证据表明，miR-429 参与了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。肝再生是一个高度协调的过程，可以被 microRNAs（miRNAs）调控，尽管其机制在很大程度上尚不清楚。在本研究中，我们旨在确定 miR-429 在肝再生过程中对肝细胞增殖的作用。首先，我们进行了微阵列分析和 qRT-PCR。结果表明，部分肝切除后 30 小时大鼠肝组织中 miR-429 水平显著降低，miR-429 过表达破坏了 BRL-3A 增殖以及大鼠肝细胞从 G1 期向 S 期的转化，并促进了肝细胞凋亡。相比之下，miR-429 下调则具有相反的效果。miR-429 在体外和体内均负调控 JUN 的表达。使用 JUN siRNA 后，我们发现 JUN 抑制介导了 miR-429 在肝细胞增殖和生长中的作用，并且 miR-429 负调控 JUN/MYC/BCL2/CCND1 信号通路。我们的结果还表明，miR-429 通过靶向 JUN/MYC/BCL2/CCND1 抑制肝细胞增殖和肝再生。
