M1C Mediates LINE-1 Transcription in PARP Inhibitor-Treated Prostate Cancer Cells - PubMed
7 days ago
- #PARP Inhibitors
- #Prostate Cancer
- #Retrotransposons
- M1C protein is induced by olaparib treatment in HR-competent CRPC cells.
- M1C drives ATM expression, KAP1(S824) phosphorylation, and STING activation, leading to LINE-1 (L1) retrotransposon derepression.
- M1C is necessary for the induction of L1-5'UTR, L1-ORF1, L1-ORF2 transcripts, and ORF1p RNA binding protein.
- M1C also activates HERV-K102/108 gag, pol, and env genes, along with HERV-K ENV protein expression.
- M1C integrates L1 and HERV-K activation with APOBEC3 (A3) gene induction, which restrains retrotransposon-induced genomic instability.
- M1C is essential for inducing L1, HERV-K, and A3 expression, contributing to olaparib resistance in CRPC cells.
- M1C is a potential therapeutic target for HR-competent CRPC treated with PARP inhibitors.