Circular RNA circPSD3 alleviates hepatic fibrogenesis by regulating the miR-92b-3p/Smad7 axis

Area of Science:

• Molecular Biology
• Hepatology
• Biochemistry

Background:

• Circular RNAs (circRNAs) are increasingly linked to hepatocellular carcinoma (HCC).
• The role of circRNAs in hepatic fibrosis (HF) remains largely unexplored.
• circPSD3 expression was found downregulated in carbon tetrachloride (CCl4)-induced HF models.

Purpose of the Study:

• To investigate the function of circRNAs, specifically circPSD3, in hepatic fibrosis (HF).
• To elucidate the underlying molecular mechanism of circPSD3 in regulating hepatic fibrogenesis.
• To assess the potential of circPSD3 as a biomarker for HF.

Main Methods:

• Utilized a carbon tetrachloride (CCl4)-induced mouse model of hepatic fibrosis (HF).
• Employed in vivo overexpression of circPSD3 using adeno-associated virus serotype 8 (AAV8).
• Conducted in vitro loss-of-function and gain-of-function assays on hepatic stellate cells (HSCs).
• Performed molecular analyses including miRNA sponging and gene expression studies.

Main Results:

• Overexpression of circPSD3 in vivo ameliorated CCl4-induced HF, reducing liver injury markers (ALT, AST) and fibrotic indicators (hydroxyproline, collagen deposition).
• circPSD3 significantly inhibited the activation and proliferation of hepatic stellate cells (HSCs) in vitro.
• Mechanistically, circPSD3 acts as a molecular sponge for miR-92b-3p, leading to the upregulation of Smad7 expression.

Conclusions:

• circPSD3 plays a protective role in alleviating hepatic fibrogenesis.
• The mechanism involves circPSD3 targeting the miR-92b-3p/Smad7 axis.
• circPSD3 demonstrates potential as a novel therapeutic target and diagnostic biomarker for hepatic fibrosis.