RNF213 inhibits migration via mediating KRT16 ubiquitination in lung adenocarcinoma cell

Abstract Background Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors, and lung adenocarcinoma (LUAD) accounts for 40% of NSCLC. Ring finger protein 213(RNF213) has been shown to inhibit the progression of many different cancers including glioblastoma and breast cancer. However, the role of RNF213 in LUAD has not been reported. The aim of this study was to investigate the effect of RNF213 on the progression of LUAD. Methods The expression of RNF213 in LUAD tissues was analyzed by western blot, TCGA (The Cancer Genome Atlas) and GTEx (Genotype_Tissue Expression Project) databases. Kaplan-Meier Plotter database was used to predict the clinical significance of RNF213 in LUAD. We determined the role of RNF213 in LUAD cell lines through CCK-8 assay, migration and invasion assay. The relationship of RNF213 and KRT16 were demonstrated via co-immunoprecipitation, ubiquitination, protein degradation assay and immunoblotting. We next confirmed the oncogenetic role of KRT16 using migration and rescue assay. The clinical roles of RNF213 and KRT16 were explored by immunohistochemical staining assay (IHC) and Kaplan-Meier survival analysis. Results Our data manifested that RNF213 expression was reduced in LUAD, thereby affecting the prognosis of LUAD. The molecular study revealed that RNF213 functioned by promoting KRT16 ubiquitination. IHC data analysis showed that KRT16 was negatively correlated with RNF213 protein expression, and downregulation of RNF213 was associated with poor overall survival. Conclusion RNF213 is a potential tumor suppressor that inhibits migration of LUAD cell by mediating KRT16 ubiquitination.