The Mitochondrial Protein C1QBP Promotes Hepatocellular Carcinoma Progression by Enhancing Cell Survival, Migration and Invasion

Backgrounds: Hepatocellular carcinoma (HCC) is a major type of death-causing cancer whose pathological mechanisms are not fully understood. In addition, the identification of effective biomarkers for HCC prognosis is in emergency. Although a variety of studies have shown that Complement C11 binding protein (C1QBP) may play a tumor-promoting or tumor-suppressive role in cancer, the functions and mechanisms of C1QBP in HCC progression are under-investigating. Methods and results: Bioinformatic approaches were employed for checking the expression of C1QBP in HCC patient samples and the association between C1QBP mRNA expression and survival rates of patients with HCC or the promoter methylation of C1QBP. MTT analysis, PI/Annexin V staining, transwell and metabolic flux assays were performed to examine the effects of C1QBP on proliferation, apoptosis, migration, invasion, and oxidative phosphorylation of HCC cells. In the present study, we observed that C1QBP is lower expressed in HCC samples and cell lines. Moreover, high levels of C1QBP were associated with unfavorable outcomes of HCC patients. Loss-of-function assays showed that proliferation, migration and invasion of HCC cells were mitigated while cell apoptosis was augmented upon the loos of C1QBP. Moreover, the oxidative phosphorylation was moderately decreased when C1QBP was depleted. Furthermore, we also investigated the methylation status and copy number variation of C1QBP and analyzed their correlation with its mRNA expression in HCC patients. Finally, we suggested that C1QBP is correlated with genes encoding ribosome RPL-related proteins and mitochondrial MRPL-related proteins in HCC patients. Conclusions: C1QBP is correlated with a poor prognosis of HCC patients and promotes the survival, migration and invasion of HCC cells.