Jiang Wenying, Miao Yuxia, Xing Xiaoxiao, Liu Shuiqing, Xing Wei, Qian Feng
Department of Radiology, The Third Affiliated Hospital of Soochow University, Changzhou, 213000, China.
Department of Breast Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, 213000, China.
Heliyon. 2024 Mar 19;10(6):e28172. doi: 10.1016/j.heliyon.2024.e28172. eCollection 2024 Mar 30.
The MTCH2 protein is located on the mitochondrial outer membrane and regulates mitochondria-related cell death. This study set out to investigate the role of MTCH2 in the underlying pathophysiological mechanisms of breast cancer (BC). MTCH2 expression levels in BC were analyzed using bioinformatics prior to verification by cell lines in vitro. Experiments of over-expression and siRNA-mediated knockdown of MTCH2 were conducted to assess its biological functions, including its effects on cellular proliferation and cycle progression. Xenografts were utilised for study and signaling pathway alterations were examined to identify the mechanisms driven by MTCH2 in BC proliferation and cell-cycle regulation. MTCH2 was up-regulated in BC and correlated with patients' overall survival. Over-expression of MTCH2 promoted cellular proliferation and cycle progression, while silencing MTCH2 had the opposite effect. Xenograft experiments were utilised to confirm the in vitro cellular findings and it was identified that the PI3K/Akt signaling pathway was activated by MTCH2 over-expression and suppressed by its silencing. Moreover, the activation of IGF-1R rescued cellular growth and cycle arrest induced by MTCH2-silencing. Overall, this study reveals that expression of MTCH2 in BC is upregulated and potentiates cellular proliferation and cycle progression via the PI3K/Akt pathway.
MTCH2蛋白位于线粒体外膜，调节与线粒体相关的细胞死亡。本研究旨在探讨MTCH2在乳腺癌（BC）潜在病理生理机制中的作用。在通过体外细胞系验证之前，利用生物信息学分析了BC中MTCH2的表达水平。进行了MTCH2过表达和siRNA介导的敲低实验，以评估其生物学功能，包括对细胞增殖和细胞周期进程的影响。利用异种移植进行研究，并检测信号通路改变，以确定MTCH2在BC增殖和细胞周期调节中所驱动的机制。MTCH2在BC中上调，且与患者的总生存期相关。MTCH2过表达促进细胞增殖和细胞周期进程，而沉默MTCH2则产生相反的效果。利用异种移植实验证实了体外细胞实验结果，并且发现PI3K/Akt信号通路被MTCH2过表达激活，被其沉默所抑制。此外，IGF-1R的激活挽救了由MTCH2沉默诱导的细胞生长和细胞周期停滞。总体而言，本研究表明MTCH2在BC中的表达上调，并通过PI3K/Akt途径增强细胞增殖和细胞周期进程。
