1. TFAM is directly regulated by miR-23b in glioma
- Author
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Guangyong Wu, Jinfu Yang, Fei Liu, Zhifei Wang, and Jiaode Jiang
- Subjects
Cancer Research ,Carcinogenesis ,Cell ,Down-Regulation ,Biology ,medicine.disease_cause ,DNA, Mitochondrial ,Mitochondrial Proteins ,Cell Movement ,Cell Line, Tumor ,medicine ,Humans ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Regulation of gene expression ,Akt/PKB signaling pathway ,Cell growth ,Brain Neoplasms ,General Medicine ,Glioma ,Cell cycle ,TFAM ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,medicine.anatomical_structure ,Oncology ,Cancer research ,Signal Transduction ,Transcription Factors - Abstract
Mitochondrial transcription factor A (TFAM), a high-mobility group (HMG) protein, plays a central role in mitochondrial DNA (mtDNA) replication, transcription and inheritance. It has been shown that TFAM is associated with tumorigenesis. However, little is known regarding the posttranscriptional regulation of TFAM in glioma. In the present study, we found that the protein levels of TFAM were gradually increased, while the expression of miRNA-23b was gradually downregulated with the malignancy of glioma. Luciferase assay data demonstrated that miRNA-23b directly regulated TFAM. Furthermore, forced overexpression of miRNA-23b in U251 cells markedly inhibited the proliferation, cell cycle progression, migration and colony formation, while overexpression of TFAM significantly enhanced these biological processes. We further examined the related molecular mechanism, and found that the activity of the PI3K/Akt signaling pathway, critical for cell proliferation and migration, was suppressed in miRNA-23b-overexpressing U251 cells but was upregulated in TFAM-overexpressing cells. In addition, the expression levels of invasion-related MMP2 and MMP9 were decreased in miRNA-23b-overexpressing U251 cells but were increased in TFAM-overexpressing cells. Taken together, the present study provides a new regulatory mechanism as well as a promising therapy target for glioma.
- Published
- 2013