UBE2T Regulates FANCI Monoubiquitination to Promote NSCLC Progression by Activating EMT

Background: Fanconi anemia complementation group I (FANCI) acts as a critical protein factor for maintaining DNA stability. However, roles of FANCI in tumors has not been well revealed. In current study, we aimed to explore the function and potential mechanism of FANCI in non-small-cell lung cancer (NSCLC).Methods: To detect the expression of FANCI and UBE2T in NSCLC tissues, quantitative reverse-transcription PCR (qRT-PCR) and Western blot assays were employed. CCK-8, wound healing, Transwell, flow cytometry analysis and tumor xenograft were used to investigate the biological effects of FANCI in NSCLC in vitro and in vivo. FANCI binds with UBE2T was confirmed using coimmunoprecipitation (co-IP) assay. The EMT protein markers were detected via Western blot. Results: FANCI was upregulated in NSCLC tumor tissues compared with adjacent. In A549 and H1299 cells, knockdown of FANCI inhibited cell growth, migration, invasion and cell cycle,as well as epithelial-to-mesenchymal transition (EMT) in vitro. In vivo, the tumor growth was also repressed when FANCI was downregulated. Mechanistically, UBE2T directly bound with FANCI and regulated the monoubiquitination of FANCI. Futhermore, UBE2T restored the inhibitory effects induced by knocking down FANCI in NSCLC cells. Conclusion: FANCI was a putative oncogene in NSCLC, and was monouniubiquitinated by UBE2T to regulate cell growth, invasion and migration. Our findings suggested that FANCI might applied as a predicted biomarker and therapeutic target for NSCLC.