Abstract
Mounting research indicates that circRNAs are pivotal elements in tumorigenesis and progression. Understanding the mechanisms by which circRNAs function in tumors is crucial for identifying undiscovered diagnostic and treatment targets. This research centers on unraveling the mechanisms by which the novel circRNA, circFADS1, influences hepatocellular carcinoma (HCC) progression. CircFADS1 shows elevated expression in HCC and is linked to unfavorable prognosis. Functionally, circFADS1 overexpression accelerates HCC progression through inducing HCC proliferation and inhibited apoptosis. Mechanistically, RNA-seq analysis demonstrates its connection to the Wnt/β-catenin pathway. Moreover, circFADS1 interacts with GSK3β and promotes its ubiquitination and degradation by recruiting the ubiquitin ligase RNF114 while EIF4A3 facilitates the biogenesis of circFADS1. Additionally, circFADS1 is closely linked to lenvatinib resistance. Overall, this study reveals that circFADS1 regulates GSK3β function, influencing the progression of hepatocellular carcinoma. The EIF4A3/circFADS1/GSK3β/β-catenin axis is discovered to hold promise as a novel therapeutic target for hepatocellular carcinoma, while circFADS1 is also a significant factor in lenvatinib resistance.