CCDC137/DGCR8 axis promotes aerobic glycolysis in hepatocellular carcinoma via activation of the AKT/mTOR signaling pathway.

Introduction: Hepatocellular carcinoma (HCC) is a leading cause of global cancer fatality. Understanding its molecular mechanisms is crucial for developing effective treatments.

Methods: Differentially expressed genes (DEGs) in the cancer genome atlas (TCGA)-liver hepatocellular carcinoma (LIHC) and GSE101685 data sets were analyzed using the "limma" tool in R. Weighted Gene Co-expression Network Analysis (WGCNA) identified the key turquoise module. Bioinformatics analyzed the prognostic significance and expression of CCDC137. Functional analyses assessed the effects of CCDC137 on cell behavior and tumor growth. The connection between CCDC137 and DGCR8 and their impact on the AKT/mTOR signaling pathway and glycolysis were also examined.

Results: A total of 670 overlapping DEGs were identified, and CCDC137, located within the turquoise module, was found to be significantly associated with HCC. CCDC137 was upregulated in HCC, correlating with worse prognostic outcomes. Experimental validation demonstrated that CCDC137 knockdown significantly reduced HCC cell proliferation, migration, invasion, and tumor growth. Mechanistically, CCDC137 may promote aerobic glycolysis through modulation of the AKT/mTOR signaling pathway, potentially mediated via its interaction with DGCR8.

Conclusions: These findings suggest that the CCDC137/DGCR8 axis may contribute to HCC progression by regulating cellular metabolism through the AKT/mTOR pathway. Targeting this regulatory network may offer a promising direction for future therapeutic exploration in HCC.