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

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.