Oncotarget

Research Papers:

Multiple-level validation identifies PARK2 in the development of lung cancer and chronic obstructive pulmonary disease

SeungBaek Lee _, Jun She, Bo Deng, JungJin Kim, Mariza de Andrade, Jie Na, Zhifu Sun, Jason A. Wampfler, Julie M. Cunningham, Yanhong Wu, Andrew H. Limper, Marie-Christine Aubry, Chris Wendt, Peter Biterman, Ping Yang and Zhenkun Lou

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:44211-44223. https://doi.org/10.18632/oncotarget.9954

Metrics: PDF 1272 views  |   HTML 1316 views  |   ?  


Abstract

SeungBaek Lee1,*, Jun She2,3,*, Bo Deng3,4,*, JungJin Kim1,*, Mariza de Andrade3, Jie Na3, Zhifu Sun3, Jason A. Wampfler3, Julie M. Cunningham5, Yanhong Wu5, Andrew H. Limper6, Marie-Christine Aubry7, Chris Wendt8,9, Peter Biterman8, Ping Yang3, Zhenkun Lou1

1Division of Oncology Research, Mayo Clinic, Rochester, MN, USA

2Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China

3Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

4Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China

5Genomics Shared Resource, Mayo Clinic, Rochester, MN, USA

6Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA

7Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA

8Department of Medicine, Pulmonary Division, University of Minnesota, Minneapolis, MN, USA

9Department of Medicine, Pulmonary Section, Minneapolis VA Medical Center, Minneapolis, MN, USA

*These authors have contributed equally to this work

Correspondence to:

Ping Yang, email: Yang.Ping@mayo.edu

Zhenkun Lou, email: Lou.Zhenkun@mayo.edu

Keywords: lung cancer, chronic obstructive pulmonary disease, PARK2, inflammation

Received: January 27, 2016    Accepted: May 09, 2016    Published: June 13, 2016

ABSTRACT

An important precursor to lung cancer development is chronic obstructive pulmonary disease (COPD), independent of exposure to tobacco smoke. Both diseases are associated with increased host susceptibility, inflammation, and genomic instability. However, validation of the candidate genes and functional confirmation to test shared genetic contribution and cellular mechanisms to the development of lung cancer in patients with COPD remains underexplored. Here, we show that loss of PARK2 (encoding Parkin) increases the expression of proinflammation factors as well as nuclear NF-κB localization, suggesting a role of PARK2 loss in inflammation. Additional exploration showed that PARK2 deficiency promotes genomic instability and cell transformation. This role of PARK2 in inflammation and chromosome instability provides a potential link among Parkin, COPD and lung cancer. A further comprehensive validation of 114 informative single nucleotide polymorphism (SNP) variants of PARK2, in 2,484 cases and controls with well-defined lung cancer and COPD phenotypes, found rs577876, rs6455728 and rs9346917 (p<0.01) to be significantly associated with lung cancer development in people with COPD. Our findings support the evidence that PARK2 might have a tumor suppressor role in the development of COPD and lung cancer.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 9954