RNF216 as a Promising Biomarker for Prognosis, Immunotherapy, and Chemotherapy in LIHC: A Comprehensive Pan-Cancer Analysis and Experimental Validation.

BACKGROUND

RNF216 belongs to the E3 ubiquitin ligase family and plays a role in the development of various diseases. However, its systematic role in pan-cancer development has not been systematically explored.

METHODS

Publicly available data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA) were utilized. The analysis was conducted using R software and online platforms such as STRING, TISIDB, and TISCH to evaluate the role of RNF216. CCK-8 and other experiments have confirmed the function of RNF216 in liver hepatocellular carcinoma (LIHC).

RESULTS

RNF216 was significantly elevated in most tumor tissues relative to adjacent normal tissues; meanwhile, the mutation rate of RNF216 in LIHC tissues was also significantly elevated relative to normal tissues. The expression levels of RNF216 vary in tumor mutational burden (TMB) and microsatellite instability (MSI) across different tumors. It demonstrated significant diagnostic and prognostic value and was associated with clinicopathologic features in multiple cancers, especially in LIHC. The protein-protein interaction (PPI) network and GSCALite suggested that RNF216 and its co-expressed genes may promote tumor growth by regulating mitosis, cell death, and DNA damage. Gene Set Enrichment Analysis (GSEA) further revealed a positive correlation between RNF216 and cell cycle regulation pathways. RNF216 is significantly related to immune cell infiltration and expressed in various types of immune cells. Knockout of RNF216 mediated by siRNA inhibits cell proliferation and reduces the migration and invasion capability of HepG2 and Hep3B cells.

CONCLUSION

RNF216 is strongly upregulated in various tumors, including LIHC, and plays an extremely important role in tumor diagnosis and prognosis. Targeted knockout of RNF216 is beneficial for improving the efficacy of immunotherapy and chemotherapy.