MicroRNA-15a inhibits hepatic stellate cell activation and proliferation via targeting SRY-box transcription factor 9

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• MicroRNAs (miRNAs) are implicated in hepatic fibrosis (HF) progression.
• The specific role of microRNA (miR)-15a in HF remains unclear.

Purpose of the Study:

• To investigate the biological role and function of miR-15a in hepatic fibrosis.
• To elucidate the mechanism by which miR-15a influences liver fibrosis.

Main Methods:

• Assessed miR-15a expression in TGF-β1-treated LX-2 cells and CCl4-induced mouse models.
• Utilized dual-luciferase reporter assays to confirm direct targeting of SOX9 by miR-15a.
• Performed gain- and loss-of-function experiments for miR-15a and SOX9 in LX-2 cells.
• Measured cell viability, invasion, apoptosis, collagen I, and alpha smooth muscle actin (α-SMA) expression.

Main Results:

• miR-15a expression was significantly decreased in fibrotic conditions.
• miR-15a directly targets and inhibits SRY-box transcription factor 9 (SOX9) expression.
• miR-15a overexpression reduced cell viability and invasion while enhancing apoptosis.
• SOX9 overexpression reversed the effects of miR-15a, including the downregulation of collagen I and α-SMA.

Conclusions:

• miR-15a acts as a tumor suppressor in hepatic fibrosis by targeting SOX9.
• miR-15a inhibits LX-2 cell viability and hepatic fibrosis pathogenesis through SOX9 inhibition.
• miR-15a represents a potential therapeutic target for treating liver fibrosis.