Transcriptional profiling revealed the anti-proliferative effect of MFN2 deficiency and identified risk factors in lung adenocarcinoma
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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.
KeywordsMFN2 Lung adenocarcinoma Microarray The Cancer Genome Atlas
This work was supported by the National Natural Science foundation of China (81201839, 81572249, 81402378, and 81472642), the Research Project of Shanghai Municipal Commission of Health and Family Planning (20124Y108 and 201440032), the Excellent Young Teachers Program of Shanghai Jiaotong University School of Medicine, and Shanghai international cooperation project of science and technology (14430723300).
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