BPHL promotes TNBC stemness by resolving R-loops via POLR2A lactylation inhibition and BARD1-mediated ubiquitination - PubMed
5 hours ago
- #BPHL
- #Triple-Negative Breast Cancer
- #Cancer Stem Cells
- BPHL promotes TNBC stemness by resolving R-loops via POLR2A lactylation inhibition and BARD1-mediated ubiquitination.
- Low R-loop scores are a defining feature of TNBC CSCs, linked to poor prognosis and advanced tumor staging.
- BPHL overexpression expands the CSC compartment, enhances sphere formation, and accelerates tumor growth.
- BPHL engages POLR2A, reducing its lactylation and increasing BARD1-mediated ubiquitination to resolve R-loops.
- Low R-loop states are associated with enhanced intercellular communication and elevated immune checkpoint gene expression.
- BPHL depletion curbs tumorigenesis, with effects mitigated by RNase H overexpression and reinstated by β-catenin blockade.