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miR-29a-3p suppresses hepatic fibrosis pathogenesis by modulating hepatic stellate cell proliferation via targeting PIK3R3 gene expression.

Abstract：

OBJECTIVE:Hepatic stellate cells (HSC) activation and proliferation mediated the pathogenic development of hepatic fibrosis (HF). However, the underlying mechanisms remain poorly understood. In this study, we aimed to investigate the miR-29a-3p and its effects on PIK3R3 expression in HF pathogenesis. METHODS:LX-2 cells treated with TGF-β1 was used as the in vitro HF model. The expression of microRNAs and proteins in LX-2 cells were detected by quantitative RT-PCR and western blotting. Then, miR-29a-3p expression in LX-2 cells were altered via transfection with specific mimics or inhibitors, followed by cell proliferation measured through CCK-8, Edu staining and colony formation. The dual luciferase reporter assay was done to assess binding of miR-29a-3p with PIK3R3 gene sequences. Moreover, PIK3R3 gene overexpression in LX-2 cell was realized through transfection with recombinant pcDNA3.0-PIK3R3 plasmids. RESULTS:Successful establishment of cellular HF model was validated through the increased Col-I and a-SMA expression in TGF-β1-treated LX-2 cells shown by qRT-PCR and Western blot. In such model, miR-29a-3p expression in LX-2 cells showed the greatest decrease among four candidate microRNAs in response to TGF-β1 treatment. Also, miR-29a-3p directly binds with the 3' UTR region of the PIK3R3 gene to suppress its expression in LX-2 cells. Furthermore, PIK3R3 gene overexpression effectively abrogated the changes of LX-2 cell proliferation, AKT phosphorylation and Col-I and a-SMA expression caused by miR-29a-3p mimics. CONCLUSION:MiR-29a-3p regulates hepatic stellate cell proliferation and hepatic fibrosis pathogenesis by targeting PIK3R3 expression and modulating the PI-3K/AKT signaling.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Fu J,Wu B,Zhong S,Deng W,Lin F

doi

10.1016/j.bbrc.2020.06.102

subject

Has Abstract

pub_date

2020-09-03 00:00:00

pages

922-929

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(20)31320-6

journal_volume

529

pub_type

杂志文章

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miR-29a-3p suppresses hepatic fibrosis pathogenesis by modulating hepatic stellate cell proliferation via targeting PIK3R3 gene expression.