Down-regulation of MiR-127 facilitates hepatocyte proliferation during rat liver regeneration.
Liver regeneration (LR) after partial hepatectomy (PH) involves the proliferation and apoptosis of hepatocytes, and microRNAs have been shown to post-transcriptionally regulate genes involved in the regulation of these processes. To explore the role of miR-127 during LR, the expression patterns of miR-127 and its related proteins were investigated. MiR-127 was introduced into a rat liver cell line to examine its effects on the potential target genes Bcl6 and Setd8, and functional studies were undertaken. We discovered that miR-127 was down-regulated and inversely correlated with the expression of Bcl6 and Setd8 at 24 hours after PH, a time at which hypermethylation of the promoter region of the miR-127 gene was detected. Furthermore, in BRL-3A rat liver cells, we observed that overexpression of miR-127 significantly suppressed cell growth and directly inhibited the expression of Bcl6 and Setd8. The results suggest that down-regulation of miR-127 may be due to the rapid methylation of its promoter during the first 24 h after PH, and this event facilitates hepatocyte proliferation by releasing Bcl6 and Setd8. These findings support a miRNA-mediated negative regulation pattern in LR and implicate an anti-proliferative role for miR-127 in liver cells.
Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China.
Chuanyong
C
Pan
Huan
H
Chen
Lianghua
L
Wang
Shengsheng
S
Yang
Hailong
H
Fu
Yongxia
Y
Zheng
Mingyong
M
Miao
Binghua
B
Jiao
D000818:Animals; D049109:Cell Proliferation; D018899:CpG Islands; D019175:DNA Methylation; D015536:Down-Regulation; D022781:Hepatocytes / Q000166:cytology*; D008115:Liver Regeneration; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic; D051381:Rats
D035683:MicroRNAs; C544526:Mirn127 microRNA, rat