HDAC2-Mediated METTL3 Delactylation Promotes DNA Damage Repair and Chemotherapy Resistance in Triple-Negative Breast Cancer.

ABSTRACT: The current treatment of triple-negative breast cancer (TNBC) is still primarily based on platinum-based chemotherapy. However, TNBC cells frequently develop resistance to platinum and experience relapse after drug withdrawal. It is crucial to specifically target and eliminate cisplatin-tolerant cells after platinum administration. Here, it is reported that upregulated N ⁶-methyladenosine (m⁶A) modification drives the development of resistance in TNBC cells during cisplatin treatment. Mechanistically, histone deacetylase 2 (HDAC2) mediates delactylation of methyltransferase-like 3 (METTL3), facilitating METTL3 interaction with Wilms'-tumor-1-associated protein and subsequently increasing m⁶A of transcript-associated DNA damage repair. This ultimately promot

SUBMITTER: He X 

PROVIDER: S-EPMC11984901 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature