CircSMEK1 Suppresses HCC via the hnRNPK-IGF2-AKT Axis: A Diagnostic Biomarker and Therapeutic Target.

ABSTRACT: The mechanism underlying metabolic dysfunction-associated steatohepatitis (MASH) to hepatocellular carcinoma (HCC) is elusive, and whether circRNA can serve as biomarker or therapeutic target for MASH/HCC needs to be systematically explored. Integrative transcriptomic analysis of circRNA from MASH and HCC were performed. Multi-cohort analyses of serum and tissues from MASH and HCC patients (n = 206) were conducted. Mechanisms are explored via RNA-protein interaction assays, CRISPR-mediated knockdown, and xenograft/PiggyBac-mediated mice models. circSMEK1 is significantly decreased in MASH/HCC tissues and serum, correlating with tumor size, vascular invasion, and overall survival. Mechanistically, nuclear circSMEK1 binds hnRNPK, promoting its ubiquitin-mediated degradation, suppressing IGF2

SUBMITTER: Guo P 

PROVIDER: S-EPMC12752665 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature