Abstract
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.
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Data availability
He datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Statement regarding the use of third parties to generate data: No third parties were used to generate data in the present study.
Code availability
Not applicable.
Abbreviations
- TFB1M:
-
Mitochondrial transcription factor B1
- HCC:
-
Hepatocellular carcinoma
- EMT:
-
Epithelia-mesenchymal transition
- PET:
-
Positron emission tomography
- OXPHOS:
-
Oxidative phosphorylation
- TFAM:
-
Mitochondria transcription factor A
- TCGA:
-
The cancer genome atlas
- siRNAs:
-
Small interference RNAs
- cDNA:
-
Complementary DNA
- PVDF:
-
Polyvinylidene difluoride
- H&E:
-
Hematoxylin and eosin
- IHC:
-
Immunohistochemical
- miRNAs:
-
MicroRNAs
- AML:
-
Acute myeloid leukemia
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Funding
This study was supported by the National Natural Science Foundation of China (Grant 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). Young Scientists Fund, 81802345, Peng Yuan.
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JM, ZW and FL performed most of the experiments and analyzed data; RT, BZ and PQ participated in the in vitro and vivo study. HZ and JY designed the overall study, supervised the experiments. JM and YT wrote the paper. YT and PY revised the paper. PY and HZ acquired the funding. All authors read and approved the final manuscript.
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Mu, J., Tian, Y., Liu, F. et al. Mitochondrial transcription factor B1 promotes the progression of hepatocellular carcinoma via enhancing aerobic glycolysis. J. Cell Commun. Signal. 16, 223–238 (2022). https://doi.org/10.1007/s12079-021-00658-8
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DOI: https://doi.org/10.1007/s12079-021-00658-8