Abstract
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer and has a poor prognosis. RBR E3 ubiquitin ligases are a special class of E3 ubiquitin ligases which contain three zinc-bing domains that catalyze ubiquitin to substrate proteins. The RBR family of E3 ubiquitin ligases has been reported in various human malignancies, but the roles of RBR E3 ubiquitin ligases in LUAD remain unclear. METHODS: By using TCGA and Kaplan-Meier plotter databases, we examined the expression and prognostic value of RBR E3 ubiquitin ligases. cBioPortal was used to analyze genetic mutations. The STRING database was used to build a protein interactive network. GO, KEGG, and GSEA were performed to investigate the potential biological functions of RBR E3 ubiquitin ligases. RESULTS: The expression of ARIH2, RNF144B, RNF216, and RNF217 was significantly related to the clinicopathological parameters and prognosis in LUAD patients. GSEA enrichment result showed ARIH2, RNF144B, RNF216, and RNF217 were all associated with NADH dehydrogenase complex assembly. GO functional enrichment analysis revealed that four RBR E3 ubiquitin ligases and their interactors were most correlated with ubiquitin-protein transferase activity. KEGG pathway analysis indicated they were associated with cytosolic DNA-sensing pathway, RIG-I-like receptor signaling pathway and NF-kappa B signaling pathway. CONCLUSIONS: Our comprehensive bioinformatic analysis revealed that ARIH2, RNF144B, RNF216, and RNF217 may be new prognostic biomarkers and these findings will help to better understand the distinct roles of RBR E3 ubiquitin ligases in LUAD.