The oncogenic role of TIMM8A in cancer and the mechanistic insights into the function in breast cancer cells

作者：Weiwei Wang, Mengjie Liu, Huizi Wu, Lee Jia, Wei Lv, Chaofan Li, Chong Du, Feng Cong, Yu Zhang, Yifan Cai, Yiwei Jia, Yijian Hu, Jingkun Qu, Shuqun Zhang, Fei Wu · 发表于：Scientific Reports · 年份：2025 · DOI：10.1038/s41598-025-03331-x · 被引用次数：2 · 研究领域：Galectins and Cancer Biology、Ubiquitin and proteasome pathways、Protease and Inhibitor Mechanisms

The expression of TIMM8A, a molecular chaperone involved in mitochondrial protein translocation, was observed to be significantly elevated in various tumor types. However, the specific role of TIMM8A in cancer development and its underlying molecular mechanism remains inadequately understood. In this study, our primary objective was to investigate the functional implications of TIMM8A in breast cancer development, while also assessing its expression levels and prognostic relevance in pan-cancer. Notably, TIMM8A exhibited high expression in nearly 33 different cancer types, which was consistently associated with unfavorable clinical outcomes. In breast cancer, TIMM8A exhibited a strong association with prognosis and demonstrated its potential as an independent prognostic indicator. Additionally, the inhibition of TIMM8A effectively impeded the proliferation of MCF-7 and MDA-MB-231 cells, while also suppressing their migratory and invasive capabilities in vitro. Mechanistically, the downregulation of NF-κB p65, upregulation of pro-apoptotic proteins, and regulation of EMT-related proteins were observed upon TIMM8A knockdown. Furthermore, the over-expression of miR-10b-5p effectively hindered the expression of TIMM8A. Collectively, TIMM8A, a critical oncogene, was regulated by miR-10b-5p and could activate NF-κB signaling cascade response, promote apoptosis inhibition and regulate EMT-related protein expression, thereby stimulating proliferation, migration, and invasion of breas...