miR375 affects the hedgehog signaling pathway by downregulating RAC1 to inhibit hepatic stellate cell viability and epithelialmesenchymal transition.
Mol Med Rep
; 23(3)2021 03.
Article
in En
| MEDLINE
| ID: mdl-33398380
ABSTRACT
MicroRNAs (miRNAs/miRs) are a class of noncoding RNAs that serve crucial roles in liver cancer and other liver injury diseases. However, the expression profile and mechanisms underlying miRNAs in liver fibrosis are not completely understood. The present study identified the novel miR375/Rac family small GTPase 1 (RAC1) regulatory axis in liver fibrosis. Reverse transcriptionquantitative PCR was performed to detect miR375 expression levels. MTT, flow cytometry and western blotting were performed to explore the in vitro roles of miR375. The dualluciferase reporter gene assay was performed to determine the potential mechanism underlying miR375 in liver fibrosis. miR375 expression was significantly downregulated in liver fibrosis tissues and cells compared with healthy control tissues and hepatocytes, respectively. Compared with the prenegative control group, miR375 overexpression inhibited mouse hepatic stellate cell (HSC) viability and epithelialmesenchymal transition, and alleviated liver fibrosis. The dualluciferase reporter assay results demonstrated that miR375 bound to RAC1. Moreover, the results indicated that miR375 regulated the hedgehog signaling pathway via RAC1 to restrain HSC viability and EMT, thus exerting its antiliver fibrosis function. The present study identified the miR375/RAC1 axis as a novel regulatory axis associated with the development of liver fibrosis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
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Rac1 GTP-Binding Protein
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MicroRNAs
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Hedgehog Proteins
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Hepatic Stellate Cells
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Epithelial-Mesenchymal Transition
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Liver Cirrhosis
Limits:
Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Mol Med Rep
Year:
2021
Document type:
Article