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08 January 2016 : Animal Research  

MicroRNA-21 Contributes to Liver Regeneration by Targeting PTEN

Xiaoyu ChenBCD, Meiyi SongABC, Wei ChenDE, Jasmina Dimitrova-ShumkovskaBE, Yingying ZhaoBCD, Yan CaoBCD, Yang SongCF, Wenzhuo YangB, Fei WangB, Yang XiangAB, Changqing YangAEG

DOI: 10.12659/MSM.896157

Med Sci Monit 2016; 22:83-91

Abstract

BACKGROUND: Multiple 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 AND METHODS: miR-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.

RESULTS: A 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.

CONCLUSIONS: miR-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.

Keywords: Cell Size, Gene Expression Profiling, Hepatectomy, Hepatocytes - cytology, Liver - physiology, Liver Regeneration, Mice, Inbred C57BL

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750