MicroRNA-21 Contributes to Liver Regeneration by Targeting PTEN

Abstract

BackgroundMultiple microRNAs (miRNAs, miRs), including miR-21, have been documented to be critical regulators of liver regeneration, but the mechanism underlying their roles in hepatocyte proliferation and cell cycle progression is still far from understood.Material/MethodsmiR-21 levels were determined using qRT-PCRs in mouse livers at 48 h after 70% partial hepatectomy (PH-48 h). Cell proliferation was determined by use of a cell-counting kit-8 (CCK-8), EdU incorporation staining, and flow cytometry. Phosphatase and tensin homolog (PTEN) expressions were determined using qRT-PCR and Western blot analysis. PTEN siRNA was used to perform the rescue experiment.ResultsA marked upregulation of miR-21 was observed in mouse livers at 48 h after 70% partial hepatectomy (PH-48 h) compared to 0 h after PH (PH-0 h). Overexpression of miR-21 was associated with increased proliferation and a rapid G1-to-S phase transition of the cell cycle in BNL CL.2 normal liver cells in vitro. In addition, we showed that PTEN expression was inversely correlated with miR-21 in BNL CL.2 cells and demonstrated that PTEN expression is lower in mouse livers at PH-48 h. Moreover, the presence of PTEN siRNA significantly abolished the suppressive effect of miR-21 inhibitor on hepatocyte proliferation.ConclusionsmiR-21 overexpression contributes to liver regeneration and hepatocyte proliferation by targeting PTEN. Upregulation of miR-21 might be a useful therapeutic strategy to promote liver regeneration.

PTEN Down‐Regulation Promotes β‐Oxidation to Fuel Hypertrophic Liver Growth After Hepatectomy in Mice

“…No direct evidence supports a role for PTEN in liver regeneration to date. However, the proregenerative functions of several microRNAs have been associated with suppression of PTEN after resection …”

MicroRNA-21-Regulated Activation of the Akt Pathway Participates in the Protective Effects of H₂S against Liver Ischemia–Reperfusion Injury

“…6). Administration of GYY4137, a water-soluble and slow-releasing H 2 S donor, 16) acts as an exogenous H 2 S donor to the rats, leading to the activation of Akt pathway through inhibiting PTEN in a miR-21-dependent manner, 12,13) since anti-miR-21 could partially abolish the protective effects of H 2 S against liver I/R. Activated Akt inhibits the activation of GSK3β through increasing its phosphorylation, 31) lead- ing to reduced caspase-9 activation and sequential caspase-3 inhibition.…”

“…21) By downregulating PTEN, miR-21 promotes the activation of the Akt pathway. 13,19) However, exogenous H 2 S could restore the activation of Akt pathway by downregulating PTEN via increasing the expression of miR-21. The regulatory effect of miR-21 on the expression of PTEN has been validated by using luciferase reporter assays in BRL cells.…”

“…10,11) On the other hand, microRNA-21 (miR-21) serves as an activator for the Akt pathway by regulating the expression of phosphatase and tensin homolog (PTEN), 12,13) and also exhibits anti-inflammatory and anti-apoptotic effects. 14,15) Nevertheless, the role of miR-21 in mediating the protective effects of H 2 S in hepatic I/R-induced injury is unknown.…”

Regulation of ERK and AKT Pathways by Hepatitis B Virus X Protein via Notch1 Pathway in Hepatocellular Carcinoma

“…Real-time PCR primers are listed in Table II Transient RNA interference. Small interfering RNA (siRNA) duplexes targeting human HBx, Hes1, DUSP1, and PTEN sequences and a scrambled siRNA were designed as described previously (5,(21)(22)(23). All siRNAs were synthesized by Ribobio (Guangzhou, China).…”