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Mitofusin-2 over-expresses and leads to dysregulation of cell cycle and cell invasion in lung adenocarcinoma

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Abstract

Mitofusin-2 (MFN2) is a mitochondrial protein associated with mitochondrial fusion process. It was initially identified as a hyperplasia suppressor and implicated in Charcot–Marie–Tooth disease. Recent studies showed that MFN2 played important roles in the development of multiple tumors. Here we examined MFN2 expression in 30 lung adenocarcinoma samples and revealed that the expression of MFN2 was significantly higher in lung adenocarcinoma tissues as compared to adjacent normal tissues. We then investigated the impact of MFN2 knockdown on A549 human lung adenocarcinoma cells and showed that cell proliferation, cell cycle and invasion behavior were all deregulated by MFN2 knockdown. And deregulation of cell cycle pathway after MFN2 knockdown was confirmed by microarray analysis. Furthermore, microarray analysis also revealed that different oncogenes such as RAP1A, RALB and ITGA2 were oppositely regulated by MFN2, which provided molecular clues for the paradoxical functions of MFN2 in tumor development. Taken together, our study unraveled the tumor-promoting functions of MFN2 in lung adenocarcinoma and implicated that the role of MFN2 in cancer development might be more complicated than expected and should be explored in detail in the future.

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Acknowledgments

This work was supported by the National Natural Science foundation of China (81201839 and 81101770), the Research Project of Shanghai Municipal Commission of Health and Family Planning (20124Y108), the Excellent Young Teachers Program of Shanghai Jiaotong University School of Medicine, the Science and Technology Foundation of Shanghai Chest Hospital (YZ12-03) and the National High Technology Research and Development Program (2008AA02Z441).

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    Authors and Affiliations

    1. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, 241 West Huaihai Road, Shanghai, 200030, People’s Republic of China

      Yuqing Lou, Rong Li, Yanwei Zhang, Xueyan Zhang, Bo Jin, Hua Zhong & Baohui Han

    2. Department of Hypertension Research, Beijing Anzhen Hospital, Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, 2 Anzhen Road, Beijing, 100029, People’s Republic of China

      Jielin Liu, Ya Liu, Zuoguang Wang & Shaojun Wen

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    1. Yuqing Lou
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    Correspondence to Shaojun Wen or Baohui Han.

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    Yuqing Lou, Rong Li have contributed equally to this work.

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    Lou, Y., Li, R., Liu, J. et al. Mitofusin-2 over-expresses and leads to dysregulation of cell cycle and cell invasion in lung adenocarcinoma. Med Oncol 32, 132 (2015). https://doi.org/10.1007/s12032-015-0515-0

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