CircDock6 drives metabolic dysfunction-associated steatotic liver disease progression in mice and mouse hepatocytes via mmu-let-7g-5p/insulin-like growth factor 1 receptor regulation.

Abstract

ObjectiveCircular RNAs belong to a category of noncoding RNAs that feature a unique continuous, covalently bonded ring configuration. Recent research indicates that circular RNAs are essential for the development of metabolic dysfunction-associated steatotic liver disease. This study sought to examine the functional role and molecular mechanism of circDock6 in metabolic dysfunction-associated steatotic liver disease.MethodsQuantitative reverse transcription polymerase chain reaction was performed to determine circDock6 expression patterns in liver tissues from high-fat diet- and standard diet-fed mice in vivo. Triglyceride detection, western blot analysis, and oil red O staining were performed to evaluate the regulatory effect of circDock6 on metabolic dysfunction-associated steatotic liver disease in vitro.ResultsCircDock6 was found to be markedly overexpressed in high-fat diet liver tissues compared with that in standard diet tissues. Moreover, knockdown of circDock6 expression lowered triglyceride content and lipid droplet formation. Mechanistically, circDock6 acted as a molecular sponge for mmu-let-7g-5p, which regulated insulin-like growth factor 1 receptor expression and contributed to the progression of metabolic dysfunction-associated steatotic liver disease. CircDock6 knockdown suppressed metabolic dysfunction-associated steatotic liver disease progression by modulating insulin-like growth factor 1 receptor via mmu-let-7g-5p targeting.ConclusionOur study identified circDock6 as a novel regulator of metabolic dysfunction-associated steatotic liver disease pathogenesis through the mmu-let-7g-5p/insulin-like growth factor 1 receptor axis, indicating its potential as a therapeutic target for metabolic dysfunction-associated steatotic liver disease intervention.