This study investigates the role of Processing of Pre-RNA 1 (POP1) in triple-negative breast cancer (TNBC), a highly aggressive subtype of breast cancer with poor prognosis and limited treatment options. The authors found that POP1 is significantly up-regulated in TNBC and is associated with poor patient outcomes. In vitro and in vivo experiments demonstrated that POP1 promotes cell cycle progression and proliferation in TNBC by degrading the mRNA of CDKN1A, a key cell cycle regulator. The degradation of CDKN1A mRNA depends on the N6-methyladenosine (m6A) modification at position 497 and the recognition of this modification by YTHDF2, an m6A reader protein. Treatment with the m6A inhibitor STM2457 impaired the proliferation of POP1-overexpressing TNBC cells and improved their sensitivity to paclitaxel chemotherapy. These findings suggest that POP1 plays a crucial role in promoting TNBC proliferation by degrading CDKN1A mRNA, and that targeting m6A with STM2457 could be a promising therapeutic strategy for TNBC.This study investigates the role of Processing of Pre-RNA 1 (POP1) in triple-negative breast cancer (TNBC), a highly aggressive subtype of breast cancer with poor prognosis and limited treatment options. The authors found that POP1 is significantly up-regulated in TNBC and is associated with poor patient outcomes. In vitro and in vivo experiments demonstrated that POP1 promotes cell cycle progression and proliferation in TNBC by degrading the mRNA of CDKN1A, a key cell cycle regulator. The degradation of CDKN1A mRNA depends on the N6-methyladenosine (m6A) modification at position 497 and the recognition of this modification by YTHDF2, an m6A reader protein. Treatment with the m6A inhibitor STM2457 impaired the proliferation of POP1-overexpressing TNBC cells and improved their sensitivity to paclitaxel chemotherapy. These findings suggest that POP1 plays a crucial role in promoting TNBC proliferation by degrading CDKN1A mRNA, and that targeting m6A with STM2457 could be a promising therapeutic strategy for TNBC.