title: Downregulation of TFAM inhibits the tumorigenesis of non-small cell lung cancer by activating ROS-mediated JNK/p38MAPK signaling and reducing cellular bioenergetics.
abstract: Mitochondrial transcription factor A (TFAM) is essential for the replication, transcription and maintenance of mitochondrial DNA (mtDNA). The role of TFAM in non-small cell lung cancer (NSCLC) remains largely unknown. Herein, we report that downregulation of TFAM in NSCLC cells resulted in cell cycle arrest at G1 phase and significantly blocked NSCLC cell growth and migration through the activation of reactive oxygen species (ROS)-induced c-Jun amino-terminal kinase(JNK)/p38 MAPK signaling and decreased cellular bioenergetics. We further found that TFAM downregulation in NSCLC cells led to increased apoptotic cell death and enhanced the sensitivity of NSCLC cells to cisplatin. Tissue microarray (TMA) data showed that elevated expression of TFAM was related to the histological grade and TNM stage of NSCLC patients. We also demonstrated that TFAM is an independent prognostic factor for overall survival of NSCLC patients. Taken together, our findings suggest that TFAM could serve as a potential diagnostic biomarker and molecular target for the treatment of NSCLC, as well as for prediction of the effectiveness of chemotherapy.
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.|Protein Quality Control and Diseases Laboratory, Attardi Institute of Mitochondrial Biomedicine, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Deyao
authors.initials: D
authors.lastname: Xie
authors.affiliation: Protein Quality Control and Diseases Laboratory, Attardi Institute of Mitochondrial Biomedicine, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Wu
authors.affiliation: Protein Quality Control and Diseases Laboratory, Attardi Institute of Mitochondrial Biomedicine, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Linhua
authors.initials: L
authors.lastname: Lan
authors.affiliation: Protein Quality Control and Diseases Laboratory, Attardi Institute of Mitochondrial Biomedicine, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Fugeng
authors.initials: F
authors.lastname: Shangguan
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Lin
authors.affiliation: Protein Quality Control and Diseases Laboratory, Attardi Institute of Mitochondrial Biomedicine, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Fuhong
authors.initials: F
authors.lastname: Chen
authors.affiliation: Protein Quality Control and Diseases Laboratory, Attardi Institute of Mitochondrial Biomedicine, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.|Huzhou Health School, Huzhou, Zhejiang 313100, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Protein Quality Control and Diseases Laboratory, Attardi Institute of Mitochondrial Biomedicine, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Protein Quality Control and Diseases Laboratory, Attardi Institute of Mitochondrial Biomedicine, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Zilei
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Kate
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Protein Quality Control and Diseases Laboratory, Attardi Institute of Mitochondrial Biomedicine, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Song
authors.affiliation: Protein Quality Control and Diseases Laboratory, Attardi Institute of Mitochondrial Biomedicine, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Yongzhang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Protein Quality Control and Diseases Laboratory, Attardi Institute of Mitochondrial Biomedicine, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C499631:TFAM protein, human; D014157:Transcription Factors; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: TFAM; cellular bioenergetics; chemosensitivity; mitochondria; non-small cell lung cancer
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