The m(6)A reader YTHDF3 promotes TNBC progression by regulating CENPI stabilization.

BACKGROUND: RNA N (6)-methyladenosine (m(6)A) readers mediate cancer progression. However, the role of eiptranscriptomic modifications such as m(6)A in the regulation of TNBC progression is unclear. METHODS: High-throughput library screening identifies the key m(6)A regulator YTHDF3 in TNBC. Cell and animal experiments were used to identify that YTHDF3 promoted TNBC tumorigenesis to enhance Centromere protein I (CENPI) translation via m(6)A modification. RESULTS: We showed that the N (6)-methyladenosine (m(6)A) reader YTHDF3 was an independent risk factor in TNBC and was associated with poor prognosis of patients. Notedly, overexpression YTHDF3 promoted TNBC tumorigenesis in an m(6)A modification, while TNBC knockdown markedly inhibited proliferation and migratory ability of tumor cells in vitro and in vivo. Mechanistically, Mechanistically, YTHDF3 interacted with Centromere protein I (CENPI) mRNAs to prolong stability of m(6)A-modified RNA. CONCLUSION: Our findings indicated that m(6)A reader YTHDF3 contributed to tumorigenesis and poor prognosis, providing a potential prognostic biomarker and therapeutic target for TNBC.