Abstract
Liver regeneration is a highly orchestrated process which can be regulated by microRNAs (miRNAs, miRs), though the mechanisms are largely unclear. This study was aimed to identify miRNAs responsible for hepatocyte proliferation during liver regeneration. Here we detected a marked elevation of miR-382 in the mouse liver at 48 hrs after partial hepatectomy (PH-48h) using microarray analysis and qRT-PCRs. miR-382 overexpression accelerated the proliferation and the G1 to S phase transition of the cell cycle both in mouse NCTC1469 and human HL7702 normal liver cells, while miR-382 downregulation had inverse effects. Moreover, miR-382 negatively regulated PTEN expression and increased Akt phosphorylation both in vitro and in vivo. Using PTEN siRNA and Akt activator/inhibitor, we further found that PTEN inhibition and Akt phosphorylation were essential for mediating the promotive effect of miR-382 in the proliferation and cell growth of hepatocytes. Collectively, our findings identify miR-382 as a promoter for hepatocyte proliferation and cell growth via targeting PTEN-Akt axis which might be a novel therapeutic target to enhance liver regeneration capability.
Highlights
Liver possesses a tremendous regenerative capability after injury or surgical resection [1, 2]
As PTEN is an inhibitor for Akt phosphorylation, we further investigated whether Akt contributes to the promotive effect of miR-382 on hepatocyte proliferation and cell growth
Liver regeneration after partial hepatectomy (PH) is principally mediated by the proliferation of hepatocytes which can be impacted by dysregulated miRNAs, though the underlying molecular mechanisms are still largely unclear
Summary
Liver possesses a tremendous regenerative capability after injury or surgical resection [1, 2]. MiRNAs have increasingly been reported to control the process of liver regeneration [11, 12]. Among the aberrantly expressed miRNAs, miR-21 [11, 13,14,15], -23b [16], -122 [17], -203 [18] and -221 [19] have been shown as promoters for hepatocyte proliferation, while miR-26a [20], -33 [21], -34a [22], -127 [23], -150 [24] and -378 [11] have inverse effect. The mechanisms mediating the regulatory effect of miRNAs in liver regeneration are still largely unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
