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

doi:10.1016/j.isci.2023.108482

Comprehensive identification of onco-exaptation events in bladder cancer cell lines revealed L1PA2-SYT1 as a prognosis-relevant event

iScience. 2023 Nov 17;26(12):108482. doi: 10.1016/j.isci.2023.108482. eCollection 2023 Dec 15.

Authors

Ziwei Wang¹, Yidie Ying¹, Maoyu Wang¹, Qing Chen¹, Yi Wang¹, Xufeng Yu¹, Wei He¹, Jing Li^{2

3}, Shuxiong Zeng¹, Chuanliang Xu¹

Affiliations

¹ Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China.
² Department of Bioinformatics, Center for Translational Medicine, Naval Medical University, Shanghai 200433, China.
³ Shanghai Key Laboratory of Cell Engineering, Shanghai, China.

Abstract

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.

Keywords: Cancer; Genomics; Molecular mechanism of gene regulation; Transcriptomics.