Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China.
PLoS One. 2011;6(5):e20238. doi: 10.1371/journal.pone.0020238. Epub 2011 May 31.
MicroRNAs 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 FINDING: MiR-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/SIGNIFICANCE: MiR-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.
miRNAs 是一类小的调控 RNA，调节多种生物过程，包括细胞分化、凋亡、代谢和增殖。本研究旨在探讨 miR-34a 在肝细胞增殖中的作用及其在肝再生终止中的潜在作用。
方法/主要发现：部分肝切除后 miR-34a 高度诱导。BRL-3A 细胞中 miR-34a 的过表达可显著抑制细胞增殖，并下调抑制素 βB（INHBB）和 Met 的表达。荧光素酶报告基因检测表明，INHBB 是 miR-34a 的直接靶标。更重要的是，INHBB siRNA 可显著抑制细胞增殖。在再生肝脏中检测到 INHBB 和 Met 的减少。
结论/意义：miR-34a 在肝再生的晚期表达上调。miR-34a 介导的 INHBB 和 Met 调节可能共同抑制肝细胞增殖。
