The CARM1–YIPF2 axis drives breast cancer progression and predicts poor prognosis

Abstract

Objective To investigate the roles of CARM1 and its regulatory effect on YIPF2 in breast cancer progression. Methods Breast cancer cells were transfected with CARM1 siRNA to knock down CARM1 expression. Cell proliferation, apoptosis, migration, and invasion were assessed using EdU, CCK-8, Annexin V/PI flow cytometry, wound-healing, and transwell assays, respectively. Co-expression of CARM1 and YIPF2 was evaluated using the GEPIA database and validated by qRT-PCR. Co-immunoprecipitation (Co-IP) was performed to assess the association between CARM1 and YIPF2, and asymmetric dimethylarginine (ADMA) signals in YIPF2 immunoprecipitates were assessed. Rescue experiments were performed following YIPF2 overexpression. In vivo studies were conducted to examine the anti-tumor effects of CARM1 inhibition. Results We found that CARM1 was upregulated in breast cancer patients and cell lines. Higher CARM1 expression was associated with poorer survival. CARM1 knockdown inhibited proliferation, colony formation, migration, and invasion of breast cancer cells, and induced apoptosis. The correlation analysis indicated that CARM1 and YIPF2 were positively co-expressed. Co-IP experiments supported an association between CARM1 and YIPF2. CARM1 knockdown reduced the ADMA signal in YIPF2 immunoprecipitates, consistent with CARM1-dependent YIPF2 methylation. In addition, elevated YIPF2 predicted worse survival outcomes in breast cancer patients. Overexpression of YIPF2 partially rescued the suppression of tumor progression induced by CARM1 knockdown. Finally, tumors derived from sh-CARM1 cells were markedly smaller than those from control cells. Conclusion Collectively, our findings support a role for CARM1 in breast cancer progression and provide evidence of its association with YIPF2 and CARM1-dependent YIPF2 methylation, offering insights into the CARM1–YIPF2 regulatory axis and potential therapeutic strategies.