Abstract
BackgroundMicroRNAs are a class of small regulatory RNAs that modulate a variety of biological processes, including cellular differentiation, apoptosis, metabolism and proliferation. This study aims to explore the effect of miR-34a in hepatocyte proliferation and its potential role in liver regeneration termination.Methodology/Principal FindingMiR-34a was highly induced after partial hepatectomy. Overexpression of miR-34a in BRL-3A cells could significantly inhibit cell proliferation and down-regulate the expression of inhibin βB (INHBB) and Met. In BRL-3A cells, INHBB was identified as a direct target of miR-34a by luciferase reporter assay. More importantly, INHBB siRNA significantly repressed cell proliferation. A decrease of INHBB and Met was detected in regenerating liver.Conclusion/SignificanceMiR-34a expression was upregulated during the late phase of liver regeneration. MiR-34a-mediated regulation of INHBB and Met may collectively contribute to the suppression of hepatocyte proliferation.
Highlights
The liver has a remarkable capacity to regenerate itself in response to signals as physical, chemical, nutritional, vascular, or virus-induced liver injury [1]
Despite strong evidence that miRNAs are involved in the priming and progression phase of liver regeneration (LR), little is known about how miRNAs affect the termination stage
MiR-34a is well known for its anti-oncogenic activity in several cancers, including hepatocellular carcinoma [17,19,20,21]
Summary
The liver has a remarkable capacity to regenerate itself in response to signals as physical, chemical, nutritional, vascular, or virus-induced liver injury [1]. Transforming growth factor-b is the most well-recognized candidate for the ‘stop’ signal [7,8], because it is highly expressed in the late phase of liver regeneration and can strongly inhibit hepatocyte proliferation in vitro and in vivo. Another potential candidate is activin, which belongs to the TGF-b superfamily. Activin B, a homodimer of two bB subunits encoded by the inhibin bB (INHBB) gene, is related to activin A It still remains unknown whether activin B has any roles in hepatocyte proliferation. This study aims to explore the effect of miR-34a in hepatocyte proliferation and its potential role in liver regeneration termination
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