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

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.