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1438-79482252022OctFunctional & integrative genomicsFunct Integr GenomicsOncogenic GBX2 promotes the malignant behaviors of bladder cancer cells by binding to the ITGA5 promoter and activating its transcription.937950937-95010.1007/s10142-022-00870-8In bladder cancer patients, metastasis after surgical resection and serious adverse reactions brought by cisplatin-based systemic chemotherapy make it urgent to explore novel therapeutic methods for improving the clinical outcomes of patients with unsuccessful first-line chemotherapy and disease progression. In this study, GBX2 has been recognized as a differentially expressed transcriptional factor between bladder cases with response to treatment and progressive disease based on online expression profile analysis. Higher GBX2 expression was correlated with poorer OS, DSS, and PFS in bladder cancer patients. GBX2 co-expressed genes were enriched in ECM regulation. ITGA5 was positively correlated with GBX2. GBX2 and ITGA5 were notably elevated in bladder cancer cells. GBX2 and ITGA5 similarly affected bladder cancer cell phenotypes via facilitating cell viability, migration, and invasion. By binding to the promoter region of ITGA5, GBX2 activated ITGA5 transcription, upregulating ITGA5 expression. In bladder cancer cells co-transfected with sh-GBX2 and ITGA5 oe, the inhibitory effects of GBX2 knockdown on bladder cancer cell malignant behaviors were partially eliminated by ITGA5 overexpression. In conclusion, GBX2 and ITGA5 serve as oncogenic factors, promoting the viability, migration, and invasion of bladder cancer cells. GBX2 exerts its functions by targeting the ITGA5 promoter region to activate ITGA5 transcription.© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.XiongYaoyaoYDepartment of Urology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.Extracorporeal Life Support Center of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.SongXiaohangXDepartment of Urology, Turpan People's Hospital, Turpan, 838000, Xinjiang, China.KudusiDepartment of Urology, Turpan People's Hospital, Turpan, 838000, Xinjiang, China.ZuXiongbingXDepartment of Urology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.ChenMinfengMDepartment of Urology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.HeWeiW0000-0001-8909-9008Department of Urology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. xy_heweidoctor@163.com.QiLinLDepartment of Urology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.engNo. 81802561National Natural Science Foundation of ChinaNo. 2019JJ50977Natural Science Foundation of Hunan ProvinceJournal Article20220608
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