title: TFAM is directly regulated by miR-23b in glioma.
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.
authors.affiliation: Department of Neurosurgery, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Jiaode
authors.initials: J
authors.lastname: Jiang
authors.forename: Jinfu
authors.initials: J
authors.lastname: Yang
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Wang
authors.forename: Guangyong
authors.initials: G
authors.lastname: Wu
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004272:DNA, Mitochondrial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D024101:Mitochondrial Proteins; C499631:TFAM protein, human; D014157:Transcription Factors