Mu Jiao, Tian Yiyuan, Liu Fengzhou, Wang Zijun, Tan Rui, Zhang Bei, Quan Penghe, Zhang Hongxin, Yang Jingyue, Yuan Peng
Department of Pain Treatment, Tangdu Hospital, Air Force Military Medical University, 1 Xinsi Road, Xi'an, 710038, Shaanxi, China.
Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
J Cell Commun Signal. 2022 Jun;16(2):223-238. doi: 10.1007/s12079-021-00658-8. Epub 2021 Nov 25.
Mitochondrial dysfunctions play crucial roles in the carcinogenesis of various human cancers. However, the molecular mechanisms leading to mitochondrial dysfunction and thus cancer progression remains largely unclear. TFB1M (mitochondrial transcription factor B1) is a mitochondrial DNA-binding protein that activates the transcription of mitochondrial DNA. Our bioinformatics analysis indicated a significant up-regulation of TFB1M in hepatocellular carcinoma (HCC). Here, we investigated its clinical significance and biological functions in this malignancy. Here, we found that TFB1M was significantly upregulated in HCC cells probably due to decreased miR-130a-3p expression. High TFB1M expression was positively associated with poor patient survival in HCC. TFB1M contributes to HCC growth and metastasis by promoting cell cycle progression, epithelia-mesenchymal transition (EMT), and inhibiting cell apoptosis. Mechanistically, the metabolic switch from oxidative phosphorylation to glycolysis contributed to the promotion of tumor growth and metastasis by TFB1M overexpression in HCC cells. In summary, we demonstrate that TFB1M plays a crucial oncogenic role in HCC progression, indicating TFB1M as a promising prognostic marker and therapeutic target in HCC.
线粒体功能障碍在多种人类癌症的致癌过程中起着关键作用。然而，导致线粒体功能障碍进而引发癌症进展的分子机制仍 largely 不清楚。TFB1M（线粒体转录因子 B1）是一种线粒体 DNA 结合蛋白，可激活线粒体 DNA 的转录。我们的生物信息学分析表明，TFB1M 在肝细胞癌（HCC）中显著上调。在此，我们研究了其在这种恶性肿瘤中的临床意义和生物学功能。在此，我们发现 TFB1M 在 HCC 细胞中显著上调，可能是由于 miR-130a-3p 表达降低所致。TFB1M 高表达与 HCC 患者的不良生存呈正相关。TFB1M 通过促进细胞周期进程、上皮-间质转化（EMT）和抑制细胞凋亡，促进 HCC 的生长和转移。从机制上讲，从氧化磷酸化到糖酵解的代谢转变有助于 TFB1M 在 HCC 细胞中过表达促进肿瘤生长和转移。总之，我们证明 TFB1M 在 HCC 进展中起关键致癌作用，表明 TFB1M 是 HCC 中有前景的预后标志物和治疗靶点。
