Circ-AKT3 Inhibits Malignant Progression of Hepatocellular Carcinoma by Negatively Regulating PDK1

Abstract

This study investigated the clinical and functional significance of circ-AKT3 in hepatocellular carcinoma (HCC) and its impact on tumor progression. Using qRT-PCR, we found reduced circ-AKT3 levels in HCC tissues compared to adjacent liver samples. Clinical data revealed that low circ-AKT3 expression correlated with increased lymphatic and distant metastasis. Functional experiments in MHCC-97H and Hep3B cells, chosen due to their low circ-AKT3 levels, demonstrated that circ-AKT3 overexpression suppressed HCC cell proliferation, invasion, and migration. Bioinformatics analysis and luciferase assays indicated that circ-AKT3 potentially targets PDK1. PDK1 expression was elevated in HCC tissues and cells, inversely correlated with circ-AKT3, and reduced upon circ-AKT3 overexpression. Rescue experiments illustrated that PDK1 overexpression reversed circ-AKT3-induced inhibition of HCC cell proliferation and migration. In conclusion, downregulated circ-AKT3 in HCC, associated with aggressive clinical features, hinders tumor progression by modulating PDK1. This suggests circ-AKT3′s potential as a diagnostic and prognostic biomarker for HCC.