Work

C1QBP Modulates DNA Damage Response and Radiosensitivity in Hepatocellular Carcinoma by Regulating NF-κB Activity

Year: 2025

Type: article

Abstract: C1QBP (Complement Component 1 Q Subcomponent-Binding Protein) plays a critical role in maintaining cellular metabolism, but its function in radiation-induced damage remains unclear. In this study, we generated C1QBP-deficient Huh-7 hepatocellular carcinoma (HCC) cells using CRISPR/Cas9 technology and observed that C1QBP deficiency significantly enhanced radiation-induced damage, as indicated by reduced cell proliferation, impaired colony formation, and increased γ-H2AX foci, a marker of DNA double-strand breaks. Additionally, C1QBP deficiency resulted in elevated phosphorylation of key DNA damage response (DDR) molecules, ATM and CHK2, and caused pronounced S phase cell cycle arrest. Mechanistic investigations revealed that C1QBP modulates NF-κB nuclear activity via the AMPK signaling pathway. The loss of C1QBP reduced NF-κB nuclear translocation, further exacerbating radiation-induced damage. Reintroducing C1QBP alleviated DNA damage, enhanced cell proliferation, and improved survival following radiation exposure. These findings highlight the critical role of C1QBP in modulating HCC cells radiosensitivity and underscore its potential as a therapeutic target to enhance radiotherapy outcomes.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms26104513