Comprehensive identification of onco-exaptation events in bladder cancer cell lines revealed L1PA2-SYT1 as a prognosis-relevant event
Ziwei Wang,
Yidie Ying,
Maoyu Wang,
Qing Chen,
Yi Wang,
Xufeng Yu,
Wei He,
Jing Li,
Shuxiong Zeng,
Chuanliang Xu
Affiliations
Ziwei Wang
Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
Yidie Ying
Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
Maoyu Wang
Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
Qing Chen
Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
Yi Wang
Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
Xufeng Yu
Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
Wei He
Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
Jing Li
Department of Bioinformatics, Center for Translational Medicine, Naval Medical University, Shanghai 200433, China; Shanghai Key Laboratory of Cell Engineering, Shanghai, China; Corresponding author
Shuxiong Zeng
Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China; Corresponding author
Chuanliang Xu
Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China; Corresponding author
Summary: Transposable elements (TEs) can provide ectopic promoters to drive the expression of oncogenes in cancer, a mechanism known as onco-exaptation. Onco-exaptation events have been extensively identified in various cancers, with bladder cancer showing a high frequency of onco-exaptation events (77%). However, the effect of most of these events in bladder cancer remains unclear. This study identified 44 onco-exaptation events in 44 bladder cancer cell lines in 137 RNA-seq datasets from six publicly available cohorts, with L1PA2 contributing the most events. L1PA2-SYT1, L1PA2-MET, and L1PA2-XCL1 had the highest frequency not only in cell lines but also in TCGA-BLCA samples. L1PA2-SYT1 showed significant tumor specificity and was found to be activated by CpG island demethylation in its promoter. The upregulation of L1PA2-SYT1 enhances the in vitro invasion of bladder cancer and is an independent risk factor for patient’s overall survival, suggesting L1PA2-SYT1 being an important event that promotes the development of bladder cancer.
