Exploring Vimentin's Role in Breast Cancer via PICK1 Alternative Polyadenylation and the miR-615-3p- PICK1 Interaction

Abstract Background: Breast cancer continues to be a major health issue for women worldwide, with Vimentin (VIM) identified as a crucial factor in its progression due to its role in cell migration and the epithelial-to-mesenchymal transition (EMT). This study focuses on elucidating VIM's regulatory mechanisms on the miR-615-3p/PICK1 axis, particularly through the lens of alternative polyadenylation (APA) of PICK1, and its implications for breast cancer progression. Methods:Utilizing the 4T1 breast cancer cell model, we first employed RNA-seq and proteomics to investigate changes in the APA of PICK1 following VIM knockout (KO). These high-throughput analyses aimed to uncover the underlying transcriptional and proteomic alterations associated with VIM's influence on breast cancer cells. Results: RNA-seq and proteomic profiling revealed significant APA in PICK1 following VIM KO, suggesting a novel mechanism by which VIM regulates breast cancer progression. Validation experiments confirmed that VIM KO affects the miR-615-3p-PICK1 axis, with miR-615-3p's regulation of PICK1 being contingent upon the APA of PICK1. These findings highlight the complex interplay between VIM, miR-615-3p, and PICK1 in the regulation of breast cancer cell behavior. Conclusion: This study unveils a critical role of VIM in breast cancer progression through its impact on the APA of PICK1, influencing the miR-615-3p-PICK1 axis. Our findings open new avenues for targeted therapies in breast cancer, focusing on the modulation of APA and the miR-615-3p-PICK1 interaction.