TFB1M Promotes Hepatocellular Carcinoma Growth and Metastasis by Increasing Aerobic Glycolysis

Background: Mitochondrial dysfunction plays crucial roles in the carcinogenesis of various human cancers. However, the molecular mechanism 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 bioinformatic analysis indicated a significant up-regulation of TFB1M in hepatocellular carcinoma (HCC). Here, we investigated its clinical significance and biological functions in this malignancy. Methods: The expression and clinical significance of TFB1M were determined by qRT-PCR, western blot and immunohistochemistry analysis in tissues and cell lines of HCC. The biological functions of TFB1M in HCC were determined by in vitro and in vivo cell growth and metastasis assays. Findings: Our results showed that TFB1M was significantly over-expressed in HCC cells due to the decreased miR-130a-3p expression. High TFB1M expression was associated with worse survival for HCC patients. TFB1M contributes to HCC growth and metastasis by facilitating transition of cell cycle form G1 phase to S phase, epithelia-mesenchymal transition (EMT) and inhibiting cell apoptosis. Mechanistically, metabolic switch from oxidative phosphorylation to glycolysis contributed to the promotion of tumor growth and metastasis by TFB1M overexpression in HCC cells. Interpretation: TFB1M play a crucial role in the progression of HCC, which may serve as a potential prognostic marker and treatment target in HCC.Funding Statement: This work was supported by the National Natural Science Foundation of China (grants 81802345), China Postdoctoral Science Foundation funded project (grant 2019M663984) and National Science Basic Research Plan in Shaanxi Province of China (grants 2020JM-318 and 2020JM-327).Declaration of Interests: No financial and non-financial competing interests exist in this study. Ethics Approval Statement: Informed consents have been obtained from all participants. The research was approved by the institutional ethics committee of the Air Force Military Medical University. The mice were manipulated according to the procedures approved by the Animal Ethics Committee of the Air Force Military Medical University in Xi’an, China.