Ambient fine particulate matter inhibits 15-lipoxygenases to promote lung carcinogenesis
Abstract Background Epidemiological observations have demonstrated that ambient fine particulate matter with d p < 2.5 μm (PM2.5) as the major factor responsible for the increasing incidence of lung cancer in never-smokers. However, there are very limited experimental data to support the associat...
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BMC
2019-08-01
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Series: | Journal of Experimental & Clinical Cancer Research |
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Online Access: | http://link.springer.com/article/10.1186/s13046-019-1380-z |
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doaj-a362d6757316468cab6f77995e283c81 |
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record_format |
Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ming-Yue Li Li-Zhong Liu Wende Li Calvin S. H. Ng Yi Liu Angel W. Y. Kong Zhili Zhao Shanshan Wang Haolong Qi Hao Jia Shucai Yang Jing Du Xiang Long Rocky L. K. Ho Ernest C. W. Chak Innes Y. P. Wan Tony S. K. Mok Malcolm J. Underwood Nirmal Kumar Gali Zhi Ning George G. Chen |
spellingShingle |
Ming-Yue Li Li-Zhong Liu Wende Li Calvin S. H. Ng Yi Liu Angel W. Y. Kong Zhili Zhao Shanshan Wang Haolong Qi Hao Jia Shucai Yang Jing Du Xiang Long Rocky L. K. Ho Ernest C. W. Chak Innes Y. P. Wan Tony S. K. Mok Malcolm J. Underwood Nirmal Kumar Gali Zhi Ning George G. Chen Ambient fine particulate matter inhibits 15-lipoxygenases to promote lung carcinogenesis Journal of Experimental & Clinical Cancer Research Lung cancer PM2.5 NNK 15-lipoxygenases (15-LOXs) Epigenetic and post-translational regulation |
author_facet |
Ming-Yue Li Li-Zhong Liu Wende Li Calvin S. H. Ng Yi Liu Angel W. Y. Kong Zhili Zhao Shanshan Wang Haolong Qi Hao Jia Shucai Yang Jing Du Xiang Long Rocky L. K. Ho Ernest C. W. Chak Innes Y. P. Wan Tony S. K. Mok Malcolm J. Underwood Nirmal Kumar Gali Zhi Ning George G. Chen |
author_sort |
Ming-Yue Li |
title |
Ambient fine particulate matter inhibits 15-lipoxygenases to promote lung carcinogenesis |
title_short |
Ambient fine particulate matter inhibits 15-lipoxygenases to promote lung carcinogenesis |
title_full |
Ambient fine particulate matter inhibits 15-lipoxygenases to promote lung carcinogenesis |
title_fullStr |
Ambient fine particulate matter inhibits 15-lipoxygenases to promote lung carcinogenesis |
title_full_unstemmed |
Ambient fine particulate matter inhibits 15-lipoxygenases to promote lung carcinogenesis |
title_sort |
ambient fine particulate matter inhibits 15-lipoxygenases to promote lung carcinogenesis |
publisher |
BMC |
series |
Journal of Experimental & Clinical Cancer Research |
issn |
1756-9966 |
publishDate |
2019-08-01 |
description |
Abstract Background Epidemiological observations have demonstrated that ambient fine particulate matter with d p < 2.5 μm (PM2.5) as the major factor responsible for the increasing incidence of lung cancer in never-smokers. However, there are very limited experimental data to support the association of PM2.5 with lung carcinogenesis and to compare PM2.5 with smoking carcinogens. Methods To study whether PM2.5 can contribute to lung tumorigenesis in a way similar to smoking carcinogen 4-methylnitrosamino-l-3-pyridyl-butanone (NNK) via 15-lipoxygenases (15-LOXs) reduction, normal lung epithelial cells and cancer cells were treated with NNK or PM2.5 and then epigenetically and post-translationally examined the cellular and molecular profiles of the cells. The data were verified in lung cancer samples and a mouse lung tumor model. Results We found that similar to smoking carcinogen NNK, PM2.5 significantly enhanced cell proliferation, migration and invasion, but reduced the levels of 15-lipoxygenases-1 (15-LOX1) and 15-lipoxygenases-2 (15-LOX2), both of which were also obviously decreased in lung cancer tissues. 15-LOX1/15-LOX2 overexpression inhibited the oncogenic cell functions induced by PM2.5/NNK. The tumor formation and growth were significantly higher/faster in mice implanted with PM2.5- or NNK-treated NCI-H23 cells, accompanied with a reduction of 15-LOX1/15-LOX2. Moreover, 15-LOX1 expression was epigenetically regulated at methylation level by PM2.5/NNK, while both 15-LOX1 and 15-LOX2 could be significantly inhibited by a set of PM2.5/NNK-mediated microRNAs. Conclusion Collectively, PM2.5 can function as the smoking carcinogen NNK to induce lung tumorigenesis by inhibiting 15-LOX1/15-LOX2. |
topic |
Lung cancer PM2.5 NNK 15-lipoxygenases (15-LOXs) Epigenetic and post-translational regulation |
url |
http://link.springer.com/article/10.1186/s13046-019-1380-z |
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doaj-a362d6757316468cab6f77995e283c812020-11-25T02:42:14ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-08-0138111410.1186/s13046-019-1380-zAmbient fine particulate matter inhibits 15-lipoxygenases to promote lung carcinogenesisMing-Yue Li0Li-Zhong Liu1Wende Li2Calvin S. H. Ng3Yi Liu4Angel W. Y. Kong5Zhili Zhao6Shanshan Wang7Haolong Qi8Hao Jia9Shucai Yang10Jing Du11Xiang Long12Rocky L. K. Ho13Ernest C. W. Chak14Innes Y. P. Wan15Tony S. K. Mok16Malcolm J. Underwood17Nirmal Kumar Gali18Zhi Ning19George G. Chen20Department of Surgery, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales HospitalFaculty of Medicine, Shenzhen University Health Science Center, Shenzhen UniversityGuangdong Key Laboratory of Laboratory Animal, Guangdong Laboratory Animals Monitoring InstituteDepartment of Surgery, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales HospitalDepartment of Surgery, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales HospitalDepartment of Surgery, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales HospitalDepartment of Surgery, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales HospitalDepartment of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales HospitalDepartment of Surgery, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales HospitalDepartment of Surgery, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales HospitalDepartment of Clinical Laboratory, Pingshan District People’s Hospital of ShenzhenPeking University Shenzhen HospitalPeking University Shenzhen HospitalDepartment of Surgery, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales HospitalDepartment of Surgery, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales HospitalDepartment of Surgery, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales HospitalDepartment of Clinical Oncology, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales HospitalDepartment of Surgery, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales HospitalDivision of Environment and Sustainability, The Hong Kong University of Science and TechnologyDivision of Environment and Sustainability, The Hong Kong University of Science and TechnologyDepartment of Surgery, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales HospitalAbstract Background Epidemiological observations have demonstrated that ambient fine particulate matter with d p < 2.5 μm (PM2.5) as the major factor responsible for the increasing incidence of lung cancer in never-smokers. However, there are very limited experimental data to support the association of PM2.5 with lung carcinogenesis and to compare PM2.5 with smoking carcinogens. Methods To study whether PM2.5 can contribute to lung tumorigenesis in a way similar to smoking carcinogen 4-methylnitrosamino-l-3-pyridyl-butanone (NNK) via 15-lipoxygenases (15-LOXs) reduction, normal lung epithelial cells and cancer cells were treated with NNK or PM2.5 and then epigenetically and post-translationally examined the cellular and molecular profiles of the cells. The data were verified in lung cancer samples and a mouse lung tumor model. Results We found that similar to smoking carcinogen NNK, PM2.5 significantly enhanced cell proliferation, migration and invasion, but reduced the levels of 15-lipoxygenases-1 (15-LOX1) and 15-lipoxygenases-2 (15-LOX2), both of which were also obviously decreased in lung cancer tissues. 15-LOX1/15-LOX2 overexpression inhibited the oncogenic cell functions induced by PM2.5/NNK. The tumor formation and growth were significantly higher/faster in mice implanted with PM2.5- or NNK-treated NCI-H23 cells, accompanied with a reduction of 15-LOX1/15-LOX2. Moreover, 15-LOX1 expression was epigenetically regulated at methylation level by PM2.5/NNK, while both 15-LOX1 and 15-LOX2 could be significantly inhibited by a set of PM2.5/NNK-mediated microRNAs. Conclusion Collectively, PM2.5 can function as the smoking carcinogen NNK to induce lung tumorigenesis by inhibiting 15-LOX1/15-LOX2.http://link.springer.com/article/10.1186/s13046-019-1380-zLung cancerPM2.5NNK15-lipoxygenases (15-LOXs)Epigenetic and post-translational regulation |