PARP1 Is Up-Regulated in Non-small Cell Lung Cancer Tissues in the Presence of the Cyanobacterial Toxin Microcystin
Non-small cell lung cancer (NSCLC) is the major form of lung cancer, with adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being its major subtypes. Smoking alone cannot completely explain the lung cancer etiology. We hypothesize that altered lung microbiome and chronic inflammatory insults...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2018-08-01
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Series: | Frontiers in Microbiology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2018.01757/full |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Patrick L. Apopa Lisa Alley Rosalind B. Penney Konstantinos Arnaoutakis Mathew A. Steliga Susan Jeffus Emine Bircan Banu Gopalan Jing Jin Preecha Patumcharoenpol Piroon Jenjaroenpun Thidathip Wongsurawat Nishi Shah Gunnar Boysen David Ussery Intawat Nookaew Pebbles Fagan Gurkan Bebek Gurkan Bebek Gurkan Bebek Mohammed S. Orloff Mohammed S. Orloff |
spellingShingle |
Patrick L. Apopa Lisa Alley Rosalind B. Penney Konstantinos Arnaoutakis Mathew A. Steliga Susan Jeffus Emine Bircan Banu Gopalan Jing Jin Preecha Patumcharoenpol Piroon Jenjaroenpun Thidathip Wongsurawat Nishi Shah Gunnar Boysen David Ussery Intawat Nookaew Pebbles Fagan Gurkan Bebek Gurkan Bebek Gurkan Bebek Mohammed S. Orloff Mohammed S. Orloff PARP1 Is Up-Regulated in Non-small Cell Lung Cancer Tissues in the Presence of the Cyanobacterial Toxin Microcystin Frontiers in Microbiology microbiome NSCLC lung adenocarcinoma inflammation CD36 |
author_facet |
Patrick L. Apopa Lisa Alley Rosalind B. Penney Konstantinos Arnaoutakis Mathew A. Steliga Susan Jeffus Emine Bircan Banu Gopalan Jing Jin Preecha Patumcharoenpol Piroon Jenjaroenpun Thidathip Wongsurawat Nishi Shah Gunnar Boysen David Ussery Intawat Nookaew Pebbles Fagan Gurkan Bebek Gurkan Bebek Gurkan Bebek Mohammed S. Orloff Mohammed S. Orloff |
author_sort |
Patrick L. Apopa |
title |
PARP1 Is Up-Regulated in Non-small Cell Lung Cancer Tissues in the Presence of the Cyanobacterial Toxin Microcystin |
title_short |
PARP1 Is Up-Regulated in Non-small Cell Lung Cancer Tissues in the Presence of the Cyanobacterial Toxin Microcystin |
title_full |
PARP1 Is Up-Regulated in Non-small Cell Lung Cancer Tissues in the Presence of the Cyanobacterial Toxin Microcystin |
title_fullStr |
PARP1 Is Up-Regulated in Non-small Cell Lung Cancer Tissues in the Presence of the Cyanobacterial Toxin Microcystin |
title_full_unstemmed |
PARP1 Is Up-Regulated in Non-small Cell Lung Cancer Tissues in the Presence of the Cyanobacterial Toxin Microcystin |
title_sort |
parp1 is up-regulated in non-small cell lung cancer tissues in the presence of the cyanobacterial toxin microcystin |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Microbiology |
issn |
1664-302X |
publishDate |
2018-08-01 |
description |
Non-small cell lung cancer (NSCLC) is the major form of lung cancer, with adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being its major subtypes. Smoking alone cannot completely explain the lung cancer etiology. We hypothesize that altered lung microbiome and chronic inflammatory insults in lung tissues contribute to carcinogenesis. Here we explore the microbiome composition of LUAD samples, compared to LUSC and normal samples. Extraction of microbiome DNA in formalin-fixed, paraffin-embedded (FFPE) lung tumor and normal adjacent tissues was meticulously performed. The 16S rRNA product from extracted microbiota was subjected to microbiome amplicon sequencing. To assess the contribution of the host genome, CD36 expression levels were analyzed then integrated with altered NSCLC subtype-specific microbe sequence data. Surprisingly phylum Cyanobacteria was consistently observed in LUAD samples. Across the NSCLC subtypes, differential abundance across four phyla (Proteobacteria, Bacteroidetes, Actinobacteria, and Firmicutes) was identified based on the univariate analysis (p-value < 6.4e-4 to 3.2e-2). In silico metagenomic and pathway analyses show that presence of microcystin correlates with reduced CD36 and increased PARP1 levels. This was confirmed in microcystin challenged NSCLC (A427) cell lines and Cyanobacteria positive LUAD tissues. Controlling the influx of Cyanobacteria-like particles or microcystin and the inhibition of PARP1 can provide a potential targeted therapy and prevention of inflammation-associated lung carcinogenesis. |
topic |
microbiome NSCLC lung adenocarcinoma inflammation CD36 |
url |
https://www.frontiersin.org/article/10.3389/fmicb.2018.01757/full |
work_keys_str_mv |
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doaj-dd7d61d8be274cdb9f23954448c017ee2020-11-24T21:43:46ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-08-01910.3389/fmicb.2018.01757367339PARP1 Is Up-Regulated in Non-small Cell Lung Cancer Tissues in the Presence of the Cyanobacterial Toxin MicrocystinPatrick L. Apopa0Lisa Alley1Rosalind B. Penney2Konstantinos Arnaoutakis3Mathew A. Steliga4Susan Jeffus5Emine Bircan6Banu Gopalan7Jing Jin8Preecha Patumcharoenpol9Piroon Jenjaroenpun10Thidathip Wongsurawat11Nishi Shah12Gunnar Boysen13David Ussery14Intawat Nookaew15Pebbles Fagan16Gurkan Bebek17Gurkan Bebek18Gurkan Bebek19Mohammed S. Orloff20Mohammed S. Orloff21Department of Epidemiology, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Epidemiology, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesWinthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesWinthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Epidemiology, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesCleveland Clinic, Cleveland, OH, United StatesDepartment of Epidemiology, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesCollege of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Health Behavior and Health, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Electrical Engineering and Computer Science, Case Western Reserve University, Cleveland, OH, United States0Center for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, OH, United States1Department of Nutrition, Case Western Reserve University, Cleveland, OH, United StatesDepartment of Epidemiology, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesWinthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesNon-small cell lung cancer (NSCLC) is the major form of lung cancer, with adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being its major subtypes. Smoking alone cannot completely explain the lung cancer etiology. We hypothesize that altered lung microbiome and chronic inflammatory insults in lung tissues contribute to carcinogenesis. Here we explore the microbiome composition of LUAD samples, compared to LUSC and normal samples. Extraction of microbiome DNA in formalin-fixed, paraffin-embedded (FFPE) lung tumor and normal adjacent tissues was meticulously performed. The 16S rRNA product from extracted microbiota was subjected to microbiome amplicon sequencing. To assess the contribution of the host genome, CD36 expression levels were analyzed then integrated with altered NSCLC subtype-specific microbe sequence data. Surprisingly phylum Cyanobacteria was consistently observed in LUAD samples. Across the NSCLC subtypes, differential abundance across four phyla (Proteobacteria, Bacteroidetes, Actinobacteria, and Firmicutes) was identified based on the univariate analysis (p-value < 6.4e-4 to 3.2e-2). In silico metagenomic and pathway analyses show that presence of microcystin correlates with reduced CD36 and increased PARP1 levels. This was confirmed in microcystin challenged NSCLC (A427) cell lines and Cyanobacteria positive LUAD tissues. Controlling the influx of Cyanobacteria-like particles or microcystin and the inhibition of PARP1 can provide a potential targeted therapy and prevention of inflammation-associated lung carcinogenesis.https://www.frontiersin.org/article/10.3389/fmicb.2018.01757/fullmicrobiomeNSCLClungadenocarcinomainflammationCD36 |