A LINE-1 retrotransposon promotes SEMA3C expression as a cis-regulatory enhancer to sustain breast cancer stem cell survival - PubMed
2 hours ago
- #LINE-1 retrotransposon
- #BRD4 degradation
- #breast cancer stem cells
- A LINE-1 retrotransposon (L1Md_T) acts as a cis-regulatory enhancer to drive SEMA3C expression, sustaining breast cancer stem cell (BCSC) survival in mice.
- This enhancer promotes phase-separated nuclear condensates with BRD4 under increased chromatin accessibility, enhancing SEMA3C transcription via histone H3 lysine 27 acetylation.
- SEMA3C supports BCSC self-renewal through its receptor NRP1 and coreceptors PlexinA2/PlexinD1, with the regulatory mechanism conserved in human breast cancer, involving a human LINE-1 element (SEMA3C_L1ME4a).
- Pharmacological degradation of BRD4 using the PROTAC MZ1 reduces SEMA3C levels and decreases BCSC viability, highlighting BRD4 as a therapeutic target.