Down-regulation of MiR-127 facilitates hepatocyte proliferation during rat liver regeneration.
Down-regulation of MiR-127 facilitates hepatocyte proliferation during rat liver regeneration.
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DOI：
10.1371/journal.pone.0039151
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Jiao B
中科院分区：
文献类型：
--
作者：
Pan C;Chen H;Wang L;Yang S;Fu H;Zheng Y;Miao M;Jiao B
部分肝切除术（PH）后的肝再生（LR）涉及肝细胞的增殖和凋亡，并且已经显示microRNA转录后调节参与这些过程的调节的基因。为了探讨miR-127在LR中的作用，研究了miR-127及其相关蛋白的表达模式。将miR-127导入大鼠肝细胞系以检查其对潜在靶基因Bcl 6和Setd 8的影响，并进行功能研究。我们发现，miR-127在PH后24小时下调，并与Bcl 6和Setd 8的表达呈负相关，此时检测到miR-127基因启动子区的超甲基化。此外，在BRL-3A大鼠肝细胞中，我们观察到miR-127的过表达显著抑制细胞生长，并直接抑制Bcl 6和Setd 8的表达。结果表明，miR-127的下调可能是由于其启动子在PH后的前24小时内快速甲基化，并且该事件通过释放Bcl 6和Setd 8促进肝细胞增殖。这些发现支持了LR中miRNA介导的负调控模式，并暗示了miR-127在肝细胞中的抗增殖作用。
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.
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DOI：
10.1152/ajpgi.00338.2009
发表时间：
2010-04-01
影响因子：
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作者：
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