miRNA profiles in livers with different mass deficits after partial hepatectomy and miR-106b∼25 cluster accelerating hepatocyte proliferation in rats

被引:12
作者
Xu, Xiao [1 ]
Liu, Zhikun [1 ]
Wang, Jianguo [2 ]
Ling, Qi [1 ]
Xie, Haiyang [2 ]
Guo, Haijun [2 ]
Wei, Xuyong [2 ]
Zhou, Lin [2 ]
Zheng, Shusen [1 ]
机构
[1] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Div Hepatobiliary & Pancreat Surg, Hangzhou, Zhejiang, Peoples R China
[2] Minist Publ Hlth, Key Lab Combined Multiorgan Transplantat, Beijing, Peoples R China
关键词
CELL-PROLIFERATION; MICRORNA CLUSTER; EXPRESSION; REGENERATION; FAMILY; ROLES;
D O I
10.1038/srep31267
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Partial hepatectomy (PH) promotes the reentry of quiescent hepatocytes into cell cycle for regrowth. miRNA profiles in livers with different mass deficits after PH have not been investigated and miRNAs implicated in liver regeneration remain unclear. We generated miRNA profiles from normal and remnant livers at 6, 12, 24, and 36 hours after 1/3 or 2/3PH using microarrays. Compared with normal livers, the proportion of altered miRNAs decreased with time after 1/3PH, but increased after 2/3PH. Most of altered miRNAs between 1/3 and 2/3PH exhibited similar up- or down- regulation, but lower expression magnitude for 1/3PH. Among differentially expressed miRNAs between 2/3PH with robust DNA replication and 1/3PH with a minimal replicative response, we identified miR-101a, miR-92a, miR-25, miR-93 and miR-106b as key regulators of cell cycle. In 2/3PH model, overexpression of miR-106b similar to 25 cluster tended to accelerate liver regeneration, while inhibition of miR-106b similar to 25 cluster markedly repressed regenerative response and delayed recovery of liver function. Mechanistically, RB1 and KAT2B with cell cycle arrest activity were identified as novel targets of miR-106b/93 and miR-25, respectively. Overall, we featured miRNA profiles and dynamics after 1/3 and 2/3PH, and identified miR106b similar to 25 cluster as being involved in timely cell cycle entry of hepatocytes after PH.
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页数:11
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