CCDC137 affects sorafenib resistance in hepatocellular carcinoma cells by activating the AKT/mTOR signaling pathway

Hepatocellular carcinoma (HCC) is treated with sorafenib as a first-line treatment; however, resistance reduces its clinical effectiveness. It has been demonstrated that CCDC137 influences cell survival and proliferation. However, in HCC, its role in sorafenib resistance has not been thoroughly investigated.

This study examined how CCDC137 makes HCC cells resistant to sorafenib, with a focus on the Akt/mTOR signaling pathway.

HCC cell lines resistant to sorafenib (Huh7/sora) were generated by gradually increasing sorafenib concentrations in Huh7 cells. Bioinformatics analysis was performed on the Cancer Genome Atlas (TCGA)-hepatocellular carcinoma (LIHC) dataset and the GSE29721 dataset. The prognostic significance of CCDC137 was verified using Kaplan-Meier survival curves. Using the in vitro cell assays, the consequences of CCDC137 for the migration, apoptosis, invasion, and proliferation of parental HCC cells and sorafenib-resistant cells were assessed. The changes were analyzed using the Western blot test in the AKT/mTOR signaling pathway in resistant cells after CCDC137 knockdown or overexpression.

CCDC137 was significantly elevated in Huh7/sora cells resistant to sorafenib and was linked to a poor outcome for individuals with HCC. CCDC137 knockdown reduced cell viability, induced apoptosis and inhibited migration and invasion in Huh7/sora cells. Conversely, CCDC137 overexpression in Huh7 cells enhanced sorafenib resistance. Mechanistically, CCDC137 activated the Akt/mTOR signaling pathway, AKT inhibition with MK2206 reversed opposition and increased apoptosis in resistant cells.

Through triggering the Akt/mTOR signaling pathway, CCDC137 encourages sorafenib resistance in HCC cells, potentially offering a treatment approach to combat sorafenib resistance in HCC cells.