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Down-regulation of Mitochondrial Transcription Factor A Inhibits Tumorigenesis and Enhances Chemosensitivity of Lung Adenocarcinoma A549 Cells
Wu Xiaoyi1, Lu Yuanyuan1, Hu Keke1, Lan Linhua1, Xie Deyao2, Liu Yongzhang1, Lü Bin1*
1School of Laboratory Medicine and Life Sciences, Zhejiang Provincial Key Laboratory of Medical Genetics,Wenzhou Medical University, Wenzhou 325035, China; 2Department of Cardiothoracic Surgery,the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
Abstract: The aim of this study was to investigate the effect of down-regulation of mitochondrial transcription factor A (TFAM) on lung adenocarcinoma cell line A549. A549 cells were infected with control or TFAM -shRNA lentiviral particles and the down-regulation of TFAM was confirmed by Western blot. Wound healing assay, nude mice tumorigenesis test, CCK-8 assay were carried out to examine the ability of cell migration, tumorigenesis in nude mice and cell viability of A549 cells, respectively. Our results showed that TFAM protein was significantly reduced by TFAM-shRNA plasmids. Compared with the control group, TFAM depletion cells showed a morphology change and a significant decrease in migration ability. In addition, down-regulation of TFAM led to decreased tumorigenesis of A549 cell in nude mice. Furthermore, down-regulation of TFAM enhanced cell cytotoxicity and apoptosis after treating A549 cells with a gradient doxorubicin. Taken together, our findings demonstrated that down-regulation of TFAM inhibited tumorigenesis and enhanced chemosensitivity of A549 cells, indicating that TFAM might serve as a potential target in the treatment of human lung adenocarcinoma.