N6-methyladenosine modification of DYNLT1 Facilitates Tamoxifen Resistance in Luminal B Breast Cancer

Purpose Resistance to tamoxifen poses a significant clinical challenge in the management of Luminal B breast cancer, necessitating the identification of novel biomarkers for predicting treatment response and prognosis. The specific role of DYNLT1 in endocrine response within Luminal B breast cancer remains uncertain. Methods The expression levels of DYNLT1 were assessed in breast cancer samples using immunohistochemistry, real-time PCR, and western blot analysis. The potential role of DYNLT1 in promoting resistance to tamoxifen was investigated through cell viability and colony formation assays. Furthermore, an in vivo mammary fat pad model was employed to examine the impact of DYNLT1 on tamoxifen resistance in breast tumors. Additionally, luciferase activity assays were conducted to explore the activation of the ER signaling pathway. The enrichment of ELAVL1 on mRNA of DYNLT1 was detected utilizing RNA immunoprecipitation assay. Results This study demonstrated that the DYNLT1 expression was particularly upregulated in the Luminal B subtype of breast cancer tissues. Notably, elevated DYNLT1 expression was associated with poorer relapse-free survival among Luminal B breast cancer patients treated with tamoxifen. Functionally, increased DYNLT1 expression induced resistance to tamoxifen both in vivo and in vitro . Additionally, upregulation of DYNLT1 significantly promoted ligand-independent activation of the ER signaling pathway. ELAVL1-mediated m6A modification led to overexpression of DYNLT1 and facilitated the acquisition of tamoxifen resistance phenotype. Conclusion Overall, these findings highlight that DYNLT1 could potentially act as a novel biological marker for predicting the effectiveness of tamoxifen treatment and patient prognosis in Luminal B breast cancer.