UBE2T promotes radiation resistance in non-small cell lung cancer via inducing epithelial-mesenchymal transition and the ubiquitination-mediated FOXO1 degradation. (1st December 2020)

• Record Type: Journal Article
• Authors: Yin, Hang; Wang, Xiaoyuan; Zhang, Xue; Zeng, Yangyang; Xu, Qingyong; Wang, Wenbo; Zhou, Fuxiang; Zhou, Yunfeng
• Is Part Of: Cancer letters. Volume 494(2020)
• Page Start: 121
• Page End: 131
• Publication Date: 2020-12-01
• Subjects: Lung cancer -- Radiation resistance -- UBE2T -- FOXO1 -- Ubiquitination; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2020.06.005
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Radiation resistance affects survival in non-small-cell lung cancer (NSCLC) patients. Further exploration of mechanisms and targets is urgently needed. Using bioinformatic analyses, we found that UBE2T is associated with survival, tumor size, lymph node metastasis and distant metastasis. Then, real-time PCR and immunohistochemistry were performed to explore the differentially expressed genes between normal and NSCLC tissues. Furthermore, we used colony formation, EdU incorporation, scratch, transwell assays, flow cytometry, immunofluorescence and western blot to assess the role of UBE2T in vitro and in vivo. RNA-Seq and coimmunoprecipitation were used to explore the mechanism. The results showed that UBE2T promotes proliferation, migration, invasion, and radiation resistance in vitro and in vivo by accelerating the G2/M transition and inhibiting apoptosis. Mechanistically, UBE2T promotes epithelial-mesenchymal transition (EMT) via ubiquitination-mediated FOXO1 degradation and Wnt/β-catenin signaling pathway activation. Moreover, FOXO1 reversed radiation resistance and EMT. Therefore, UBE2T may be a potential target for enhancing radiotherapy sensitivity and serve as a biomarker to predict prognosis. Highlights: UBE2T promotes epithelial-mesenchymal transition (EMT) via ubiquitination-mediated FOXO1 degradation and Wnt/β-catenin signaling pathway activation. UBE2T may be a potential target for enhancing radiotherapy sensitivity and serve as a biomarker to predict prognosis.