title: Transcriptional profiling revealed the anti-proliferative effect of MFN2 deficiency and identified risk factors in lung adenocarcinoma.
abstract: Mitofusin-2 (MFN2) was initially identified as a hyperplasia suppressor in hyper-proliferative vascular smooth muscle cells (VSMCs) of hypertensive rat arteries, which has also been implicated in various cancers. There exists a controversy in whether it is an oncogene or exerting anti-proliferative effect on tumor cells. Our previous cell cycle analysis and MTT assay showed that cell proliferation was inhibited in MFN2 deficient A549 human lung adenocarcinoma cells, without investigating the changes in regulatory network or addressing the underlying mechanisms. Here, we performed expression profiling in MFN2 knockdown A549 cells and found that cancer-related pathways were among the most susceptible pathways to MFN2 deficiency. Through comparison with expression profiling of a cohort consisting of 61 pairs of tumor-normal matched samples from The Cancer Genome Atlas (TCGA), we teased out the specific pathways to address the impact that MFN2 ablation had on A549 cells, as well as identified a few genes whose expression level associated with clinicopathologic parameters. In addition, transcriptional factor target enrichment analysis identified E2F as a potential transcription factor that was deregulated in response to MFN2 deficiency. Although bioinformatics analysis usually entail further verification, our study provided considerable information for future scientific inquiries in related areas as well as a paradigm for characterizing perturbation in regulatory network.
authors.affiliation: Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, 241 West Huaihai Road, Shanghai, 200030, People's Republic of China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Lou
authors.affiliation: Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, 241 West Huaihai Road, Shanghai, 200030, People's Republic of China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, 241 West Huaihai Road, Shanghai, 200030, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, 241 West Huaihai Road, Shanghai, 200030, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gu
authors.affiliation: Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, 241 West Huaihai Road, Shanghai, 200030, People's Republic of China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, 241 West Huaihai Road, Shanghai, 200030, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, 241 West Huaihai Road, Shanghai, 200030, People's Republic of China. zhwei2002@hotmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, 241 West Huaihai Road, Shanghai, 200030, People's Republic of China. xkyyhan@gmail.com.
authors.forename: Baohui
authors.initials: B
authors.lastname: Han
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000235:genetics*; D019295:Computational Biology; D020558:GTP Phosphohydrolases / Q000172:deficiency* / Q000235:genetics; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D024101:Mitochondrial Proteins / Q000172:deficiency* / Q000235:genetics; D051381:Rats; D012307:Risk Factors; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human
keywords: Lung adenocarcinoma; MFN2; Microarray; The Cancer Genome Atlas