Jia Xinyan, Shao Lujing, Quan Hong, Zhong Zhixian, Dong Chunyan
College of Basic Medical Science, Jinzhou Medical University, Jinzhou, Liaoning, China.
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Tongji University, Shanghai, People's Republic of China.
Biofactors. 2025 Jan-Feb;51(1):e2147. doi: 10.1002/biof.2147.
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. Utilizing the 4T1 breast cancer cell model, we first used RNA-seq and proteomics to investigate the 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. 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. This study reveals that vimentin affects the miR-615-3p-PICK1 axis through APA, revealing the key role of VIM in cancer progression. Opened up new avenues for targeted cancer therapy, with a focus on regulating the interaction between APA and miR-615-3p-PICK1.
乳腺癌仍然是全球女性面临的一个主要健康问题，波形蛋白（VIM）因其在细胞迁移和上皮-间质转化（EMT）中的作用而被确定为乳腺癌进展的关键因素。本研究聚焦于阐明VIM对miR-615-3p/PICK1轴的调控机制。利用4T1乳腺癌细胞模型，我们首先使用RNA测序和蛋白质组学来研究VIM基因敲除（KO）后PICK1的APA变化。这些高通量分析旨在揭示与VIM对乳腺癌细胞影响相关的潜在转录和蛋白质组改变。RNA测序和蛋白质组分析显示，VIM基因敲除后PICK1存在显著的APA，这表明VIM调节乳腺癌进展的一种新机制。验证实验证实，VIM基因敲除影响miR-615-3p-PICK1轴，miR-615-3p对PICK1的调节取决于PICK1的APA。这些发现突出了VIM、miR-615-3p和PICK1在调节乳腺癌细胞行为中的复杂相互作用。本研究表明波形蛋白通过APA影响miR-615-3p-PICK1轴，揭示了VIM在癌症进展中的关键作用。为靶向癌症治疗开辟了新途径，重点是调节APA与miR-615-3p-PICK1之间的相互作用。
