FNBP4 is a Potential Biomarker Associated with Cuproptosis and Promotes Tumor Progression in Hepatocellular Carcinoma

Abstract

Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors that lacks an efficient therapeutic approach because of its elusive molecular mechanisms. This study aimed to investigate the biological function and potential mechanism of formin-binding protein 4 (FNBP4) in HCC. Methods FNBP4 expression in tissues and cells were detected by quantitative real-time PCR (qRT‒PCR), Western blot, and immunohistochemistry (IHC). The Kaplan-Meier method was used to explore the correlation between the FNBP4 expression and clinical survival. MTT, EdU incorporation, colony formation, and Transwell assays were performed to evaluate the function of FNBP4 in cell proliferation and migration in vitro. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to explore the potential mechanism of FNBP4. The prognostic risk signature and nomogram were constructed to demonstrate the prognostic value of FNBP4. Results We found that FNBP4 was upregulated in patients with HCC and associated with poor overall survival (OS). Furthermore, knockdown of FNBP4 inhibited the proliferation and migration in HCC cells. Then, we performed a KEGG pathway analysis of the coexpressed genes associated with FNBP4 and found that FNBP4 may be associated with tumor-related signaling pathways and cuproptosis. We verified that FNBP4 could cause cell cycle progression and inactivation of the hippo signaling pathway. A prognostic risk signature containing three FNBP4-related differentially expressed cuproptosis regulators (DECRs) was established and can be used as an independent risk factor to evaluate the prognosis of patients with HCC. In addition, a nomogram including a risk score and clinicopathological factors was used to predict patient survival probabilities. Conclusion FNBP4, as a potential biomarker associated with cuproptosis, promotes HCC cell proliferation and metastasis. We provide a new potential strategy for HCC treatment by targeting FNBP4.

Immunomodulation of cuproptosis and ferroptosis in liver cancer

“…FNBP4 is associated with the TCA process of cuproptosis. After data analysis, it was found that the expression of FNBP4 in liver cancer increased significantly, and a high expression of FNBP4 was negatively correlated with the patient’s OS [ 78 ]. A cuproptosis-related gene (CRG) model was constructed by Ke, C. et al Through clinical sample qPCR and immunohistochemical detection, it was determined that DLAT had a cancer-promoting effect, which was significantly upregulated in liver cancer and promoted HepG2 and Huh7 cell proliferation, migration, and invasion [ 79 ].…”