Lee Hyunji, Park Jisoo, Tran Quangdon, Kim Dohoon, Hong Youngeun, Cho Hyeonjeong, Kwon So Hee, Brazil Derek, Kim Seon-Hwan, Park Jongsun
Department of Pharmacology and Medical Science, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Republic of Korea.
Mol Med Rep. 2017 Jun;15(6):3781-3786. doi: 10.3892/mmr.2017.6467. Epub 2017 Apr 12.
Mitochondrial transcription factor A (TFAM), which was initially discovered as a transcription factor for mitochondrial DNA, has known to be critical for the regulation of mitochondrial DNA. However the possible involvement of TFAM in cancer is largely unknown. In this study, we have provided some evidence that TFAM may have a potential role in brain tumor. Western blot analysis with anti‑TFAM antibody indicated that TFAM is overexpressed in glioblastoma cell lines including U87MG and U251MG. Transcriptome profiling of U87MG and U251MG cells by using deep‑sequencing revealed that TFAM transcripts were upregulated in these cells compared to its of cerebral cortex. Confocal microscopic analysis of U251MG cells with anti‑TFAM antibody showed that TFAM is located to the dot‑like structure close to nucleus, probably mitochondria and endosome. Immunohistochemical analysis of glioma tissue specimens indicated that TFAM is highly upregulated. Bioinformatical analysis with Rembrandt knowledgebase also supported that TFAM mRNA is upregulated in glioma patients. Taken together, the results presented in this study obviously provided the evidence that TFAM was upregulated in glioma cell line and glioma tissue specimens. Therefore TFAM may be a novel diagnostic marker and therapeutic target for glioma and other cancer.
线粒体转录因子A（TFAM）最初被发现是线粒体DNA的转录因子，已知其对线粒体DNA的调控至关重要。然而，TFAM在癌症中的可能作用在很大程度上尚不清楚。在本研究中，我们提供了一些证据表明TFAM可能在脑肿瘤中发挥潜在作用。用抗TFAM抗体进行的蛋白质印迹分析表明，TFAM在包括U87MG和U251MG在内的胶质母细胞瘤细胞系中过表达。通过深度测序对U87MG和U251MG细胞进行转录组分析发现，与大脑皮层相比，这些细胞中的TFAM转录本上调。用抗TFAM抗体对U251MG细胞进行共聚焦显微镜分析表明，TFAM定位于靠近细胞核的点状结构，可能是线粒体和内体。对胶质瘤组织标本进行免疫组织化学分析表明TFAM高度上调。使用伦勃朗知识库进行的生物信息学分析也支持TFAM mRNA在胶质瘤患者中上调。综上所述，本研究结果明显提供了TFAM在胶质瘤细胞系和胶质瘤组织标本中上调的证据。因此，TFAM可能是胶质瘤和其他癌症的一种新型诊断标志物和治疗靶点。
