Regulation of Wnt Singaling Pathway by Poly (ADP-Ribose) Glycohydrolase (PARG) Silencing Suppresses Lung Cancer in Mice Induced by Benzo(a)pyrene Inhalation Exposure
Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon that specifically causes cancer and is widely distributed in the environment. Poly (ADP-ribosylation), as a key post-translational modification in BaP-induced carcinogenesis, is mainly catalyzed by poly (ADP-ribose) glycohydrolase (PARG) in e...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00338/full |
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| author | Wenjuan Dai Wenjuan Dai Yingbin Fu Yanxia Deng Zhuoying Zeng Pan Gu Hailong Liu Jianjun Liu Xinyun Xu Desheng Wu Xianru Luo Linqing Yang Jinzhou Zhang Kai Lin Gonghua Hu Gonghua Hu Haiyan Huang |
| author_facet | Wenjuan Dai Wenjuan Dai Yingbin Fu Yanxia Deng Zhuoying Zeng Pan Gu Hailong Liu Jianjun Liu Xinyun Xu Desheng Wu Xianru Luo Linqing Yang Jinzhou Zhang Kai Lin Gonghua Hu Gonghua Hu Haiyan Huang |
| author_sort | Wenjuan Dai |
| collection | DOAJ |
| description | Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon that specifically causes cancer and is widely distributed in the environment. Poly (ADP-ribosylation), as a key post-translational modification in BaP-induced carcinogenesis, is mainly catalyzed by poly (ADP-ribose) glycohydrolase (PARG) in eukaryotic organisms. Previously, it is found that PARG silencing can counteract BaP-induced carcinogenesis in vitro, but the mechanism remained unclear. In this study, we further examined this process in vivo by using heterozygous PARG knockout mice (PARG+/−). Wild-type and PARG+/− mice were individually treated with 0 or 10 μg/m3 BaP for 90 or 180 days by dynamic inhalation exposure. Pathological analysis of lung tissues showed that, with extended exposure time, carcinogenesis and injury in the lungs of WT mice was progressively worse; however, the injury was minimal and carcinogenesis was not detected in the lungs of PARG+/− mice. These results indicate that PARG gene silencing protects mice against lung cancer induced by BaP inhalation exposure. Furthermore, as the exposure time was extended, the protein phosphorylation level was down-regulated in WT mice, but up-regulated in PARG+/− mice. The relative expression of Wnt2b and Wnt5b mRNA in WT mice were significantly higher than those in the control group, but there was no significant difference in PARG+/− mice. Meanwhile, the relative expression of Wnt2b and Wnt5b proteins, as assessed by immunohistochemistry and Western blot analysis, was significantly up-regulated by BaP in WT mice; while in PARG+/− mice it was not statistically affected. Our work provides initial evidence that PARG silencing suppresses BaP induced lung cancer and stabilizes the expression of Wnt ligands, PARG gene and Wnt ligands may provide new options for the diagnosis and treatment of lung cancer. |
| first_indexed | 2024-04-12T19:47:30Z |
| format | Article |
| id | doaj.art-7944555dcf6f405aa114c9a659a452da |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T19:47:30Z |
| publishDate | 2019-05-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-7944555dcf6f405aa114c9a659a452da2022-12-22T03:18:55ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-05-011010.3389/fphar.2019.00338447922Regulation of Wnt Singaling Pathway by Poly (ADP-Ribose) Glycohydrolase (PARG) Silencing Suppresses Lung Cancer in Mice Induced by Benzo(a)pyrene Inhalation ExposureWenjuan Dai0Wenjuan Dai1Yingbin Fu2Yanxia Deng3Zhuoying Zeng4Pan Gu5Hailong Liu6Jianjun Liu7Xinyun Xu8Desheng Wu9Xianru Luo10Linqing Yang11Jinzhou Zhang12Kai Lin13Gonghua Hu14Gonghua Hu15Haiyan Huang16Shenzhen Center for Disease Control and Prevention, Shenzhen, ChinaJiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, ChinaShenzhen Center for Disease Control and Prevention, Shenzhen, ChinaShenzhen Center for Disease Control and Prevention, Shenzhen, ChinaShenzhen Center for Disease Control and Prevention, Shenzhen, ChinaShenzhen Center for Disease Control and Prevention, Shenzhen, ChinaShenzhen Center for Disease Control and Prevention, Shenzhen, ChinaShenzhen Center for Disease Control and Prevention, Shenzhen, ChinaShenzhen Center for Disease Control and Prevention, Shenzhen, ChinaShenzhen Center for Disease Control and Prevention, Shenzhen, ChinaShenzhen Center for Disease Control and Prevention, Shenzhen, ChinaShenzhen Center for Disease Control and Prevention, Shenzhen, ChinaShenzhen Center for Disease Control and Prevention, Shenzhen, ChinaShenzhen Center for Disease Control and Prevention, Shenzhen, ChinaJiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, ChinaDepartment of Preventive Medicine, Gannan Medical University, Ganzhou, ChinaShenzhen Center for Disease Control and Prevention, Shenzhen, ChinaBenzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon that specifically causes cancer and is widely distributed in the environment. Poly (ADP-ribosylation), as a key post-translational modification in BaP-induced carcinogenesis, is mainly catalyzed by poly (ADP-ribose) glycohydrolase (PARG) in eukaryotic organisms. Previously, it is found that PARG silencing can counteract BaP-induced carcinogenesis in vitro, but the mechanism remained unclear. In this study, we further examined this process in vivo by using heterozygous PARG knockout mice (PARG+/−). Wild-type and PARG+/− mice were individually treated with 0 or 10 μg/m3 BaP for 90 or 180 days by dynamic inhalation exposure. Pathological analysis of lung tissues showed that, with extended exposure time, carcinogenesis and injury in the lungs of WT mice was progressively worse; however, the injury was minimal and carcinogenesis was not detected in the lungs of PARG+/− mice. These results indicate that PARG gene silencing protects mice against lung cancer induced by BaP inhalation exposure. Furthermore, as the exposure time was extended, the protein phosphorylation level was down-regulated in WT mice, but up-regulated in PARG+/− mice. The relative expression of Wnt2b and Wnt5b mRNA in WT mice were significantly higher than those in the control group, but there was no significant difference in PARG+/− mice. Meanwhile, the relative expression of Wnt2b and Wnt5b proteins, as assessed by immunohistochemistry and Western blot analysis, was significantly up-regulated by BaP in WT mice; while in PARG+/− mice it was not statistically affected. Our work provides initial evidence that PARG silencing suppresses BaP induced lung cancer and stabilizes the expression of Wnt ligands, PARG gene and Wnt ligands may provide new options for the diagnosis and treatment of lung cancer.https://www.frontiersin.org/article/10.3389/fphar.2019.00338/fullbenzo(a)pyreneADP-ribosylationpoly (ADP-ribose) glycohydrolaseWnt signaling pathwaylung cancer |
| spellingShingle | Wenjuan Dai Wenjuan Dai Yingbin Fu Yanxia Deng Zhuoying Zeng Pan Gu Hailong Liu Jianjun Liu Xinyun Xu Desheng Wu Xianru Luo Linqing Yang Jinzhou Zhang Kai Lin Gonghua Hu Gonghua Hu Haiyan Huang Regulation of Wnt Singaling Pathway by Poly (ADP-Ribose) Glycohydrolase (PARG) Silencing Suppresses Lung Cancer in Mice Induced by Benzo(a)pyrene Inhalation Exposure Frontiers in Pharmacology benzo(a)pyrene ADP-ribosylation poly (ADP-ribose) glycohydrolase Wnt signaling pathway lung cancer |
| title | Regulation of Wnt Singaling Pathway by Poly (ADP-Ribose) Glycohydrolase (PARG) Silencing Suppresses Lung Cancer in Mice Induced by Benzo(a)pyrene Inhalation Exposure |
| title_full | Regulation of Wnt Singaling Pathway by Poly (ADP-Ribose) Glycohydrolase (PARG) Silencing Suppresses Lung Cancer in Mice Induced by Benzo(a)pyrene Inhalation Exposure |
| title_fullStr | Regulation of Wnt Singaling Pathway by Poly (ADP-Ribose) Glycohydrolase (PARG) Silencing Suppresses Lung Cancer in Mice Induced by Benzo(a)pyrene Inhalation Exposure |
| title_full_unstemmed | Regulation of Wnt Singaling Pathway by Poly (ADP-Ribose) Glycohydrolase (PARG) Silencing Suppresses Lung Cancer in Mice Induced by Benzo(a)pyrene Inhalation Exposure |
| title_short | Regulation of Wnt Singaling Pathway by Poly (ADP-Ribose) Glycohydrolase (PARG) Silencing Suppresses Lung Cancer in Mice Induced by Benzo(a)pyrene Inhalation Exposure |
| title_sort | regulation of wnt singaling pathway by poly adp ribose glycohydrolase parg silencing suppresses lung cancer in mice induced by benzo a pyrene inhalation exposure |
| topic | benzo(a)pyrene ADP-ribosylation poly (ADP-ribose) glycohydrolase Wnt signaling pathway lung cancer |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.00338/full |
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