Comprehensive identification of genes driven by ERV9-LTRs reveals TNFRSF10B as a re-activatable mediator of testicular cancer cell death

摘要: The long terminal repeat (LTR) of human endogenous retrovirus type 9 (ERV9) acts as a germline-specific promoter that induces the expression proapoptotic isoform tumor suppressor homologue p63, GTAp63, in male germline cells. Testicular cancer cells silence this promoter, but inhibitors histone deacetylases (HDACs) restore GTAp63 and give rise to apoptosis. We show here numerous additional transcripts throughout genome are driven by related ERV9-LTRs. 3' Rapid amplification cDNA ends (3'RACE) was combined with next-generation sequencing establish large set such mRNAs. HDAC induce these ERV9-LTR-driven genes not LTRs from other ERVs. In particular, transcript encoding death receptor DR5 originates an ERV9-LTR inserted upstream protein coding regions TNFRSF10B gene, it shows pattern similar GTAp63. When treating testicular well ligand TNF-related apoptosis-inducing (TRAIL), rapid cell observed, which depended on expression. also cooperate cisplatin (cDDP) promote apoptosis ERV9-LTRs only drive transcripts, subset them manner. propose avoids survival damaged germ inhibition represents strategy restoring class ERV9-LTR-mediated cells, thereby re-enabling suppression.