Isochorismatase domain-containing protein 1 (ISOC1) participates in DNA damage repair and inflammation-related pathways to promote lung cancer development

Background: The advent of novel molecular targets has dramatically changed the treatment landscape of lung cancer in recent years. Isochorismatase domain-containing protein 1 (ISOC1) has been reported as a potential biomarker in gastrointestinal cancer, while its function in lung cancer has not been...

Full description

Autores:
Shi, Jinghan
Yang, Fujun
Zhou, Nanfeng
Jiang, Yan
Zhao, Yanfeng
Zhu, Junjie
Prelaj, Arsela
Malhotra, Jyoti
Normanno, Nicola
Danese, Elisa
Cardona, Andrés F.
Hong, Xuan
Jiang, Gening
Song, Xiao
Tipo de recurso:
Article of journal
Fecha de publicación:
2021
Institución:
Universidad El Bosque
Repositorio:
Repositorio U. El Bosque
Idioma:
eng
OAI Identifier:
oai:repositorio.unbosque.edu.co:20.500.12495/5848
Acceso en línea:
http://hdl.handle.net/20.500.12495/5848
https://doi.org/10.21037/TLCR-21-219
Palabra clave:
Isochorismatase domain-containing protein
miR-4633
Lung cancer
DNA damage repair
Inflammation
Rights
openAccess
License
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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network_name_str Repositorio U. El Bosque
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dc.title.spa.fl_str_mv Isochorismatase domain-containing protein 1 (ISOC1) participates in DNA damage repair and inflammation-related pathways to promote lung cancer development
dc.title.translated.spa.fl_str_mv Isochorismatase domain-containing protein 1 (ISOC1) participates in DNA damage repair and inflammation-related pathways to promote lung cancer development
title Isochorismatase domain-containing protein 1 (ISOC1) participates in DNA damage repair and inflammation-related pathways to promote lung cancer development
spellingShingle Isochorismatase domain-containing protein 1 (ISOC1) participates in DNA damage repair and inflammation-related pathways to promote lung cancer development
Isochorismatase domain-containing protein
miR-4633
Lung cancer
DNA damage repair
Inflammation
title_short Isochorismatase domain-containing protein 1 (ISOC1) participates in DNA damage repair and inflammation-related pathways to promote lung cancer development
title_full Isochorismatase domain-containing protein 1 (ISOC1) participates in DNA damage repair and inflammation-related pathways to promote lung cancer development
title_fullStr Isochorismatase domain-containing protein 1 (ISOC1) participates in DNA damage repair and inflammation-related pathways to promote lung cancer development
title_full_unstemmed Isochorismatase domain-containing protein 1 (ISOC1) participates in DNA damage repair and inflammation-related pathways to promote lung cancer development
title_sort Isochorismatase domain-containing protein 1 (ISOC1) participates in DNA damage repair and inflammation-related pathways to promote lung cancer development
dc.creator.fl_str_mv Shi, Jinghan
Yang, Fujun
Zhou, Nanfeng
Jiang, Yan
Zhao, Yanfeng
Zhu, Junjie
Prelaj, Arsela
Malhotra, Jyoti
Normanno, Nicola
Danese, Elisa
Cardona, Andrés F.
Hong, Xuan
Jiang, Gening
Song, Xiao
dc.contributor.author.none.fl_str_mv Shi, Jinghan
Yang, Fujun
Zhou, Nanfeng
Jiang, Yan
Zhao, Yanfeng
Zhu, Junjie
Prelaj, Arsela
Malhotra, Jyoti
Normanno, Nicola
Danese, Elisa
Cardona, Andrés F.
Hong, Xuan
Jiang, Gening
Song, Xiao
dc.subject.keywords.spa.fl_str_mv Isochorismatase domain-containing protein
miR-4633
Lung cancer
DNA damage repair
Inflammation
topic Isochorismatase domain-containing protein
miR-4633
Lung cancer
DNA damage repair
Inflammation
description Background: The advent of novel molecular targets has dramatically changed the treatment landscape of lung cancer in recent years. Isochorismatase domain-containing protein 1 (ISOC1) has been reported as a potential biomarker in gastrointestinal cancer, while its function in lung cancer has not been determined. Methods: The expression levels and prognostic significance of ISOC1 were assessed using bioinformatic analysis. Overexpression of ISOC1 and miR-4633, and knockdown of ISOC1 in non-small cell lung cáncer (NSCLC) cell lines were generated by lentiviral infection with overexpressed or shRNA plasmids. CRISPR/ Cas9 system was applied to knockout ISOC1 in A549 cells. The functions of ISOC1 and miR-4633 in lung cancer development were investigated using cell proliferation, migration, and invasion assays. Xenograft tumor growth assays in nude mice were further assessed the effect of ISOC1 in the tumorigenesis of NSCLC in vivo. Cell cycle distribution analysis was performed to uncover the underlying mechanism of ISOC1 and miR-4633 in promoting NSCLC cell proliferation. Co-immunoprecipitation combined with mass spectrometry and RNA sequencing were performed to uncover the potential mechanism of ISOC1 in lung cancer development. Results: Our results found that ISOC1 expression was upregulated in NSCLC tissues and that increased expression of ISOC1 was significantly associated with worse disease-free survival in NSCLC patients. Overexpression of ISOC1 could increase the proliferation, viability, migration, and invasion of NSCLC cells. Furthermore, miR-4633, located in the first intron of ISOC1, could also promote tumor cell progression and metastasis. Mice xenograft tumor assay showed that knockout of ISOC1 could significantly inhibit tumor growth in vivo. Besides, co-immunoprecipitation combined with mass spectrometry assay revealed that ISOC1 interacted with the proteins of DNA damage repair pathways and that upregulated ISOC1 expression could significantly increase the number of DNA damage lesions. RNA sequencing analysis showed that the downstream signaling pathways mediated by ISOC1 were mainly inflammation-related. Conclusions: We demonstrated that ISOC1 and its intronic miR-4633, both of them could promote NSCLC cell proliferation, migration, invasion, and cell cycle progression. ISOC1 participates in DNA damage repair and inflammation to promote lung cancer development.
publishDate 2021
dc.date.accessioned.none.fl_str_mv 2021-05-10T17:24:09Z
dc.date.available.none.fl_str_mv 2021-05-10T17:24:09Z
dc.date.issued.none.fl_str_mv 2021-03
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.local.none.fl_str_mv Artículo de revista
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dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.issn.none.fl_str_mv 2226-4477
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/20.500.12495/5848
dc.identifier.doi.none.fl_str_mv https://doi.org/10.21037/TLCR-21-219
dc.identifier.instname.spa.fl_str_mv instname:Universidad El Bosque
dc.identifier.reponame.spa.fl_str_mv reponame:Repositorio Institucional Universidad El Bosque
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identifier_str_mv 2226-4477
instname:Universidad El Bosque
reponame:Repositorio Institucional Universidad El Bosque
repourl:https://repositorio.unbosque.edu.co
url http://hdl.handle.net/20.500.12495/5848
https://doi.org/10.21037/TLCR-21-219
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.ispartofseries.spa.fl_str_mv Translational Lung Cancer Research, 2226-4477, Vol. 10, Nro. 3, 2021, p. 1444-1456
dc.relation.uri.none.fl_str_mv https://tlcr.amegroups.com/article/view/50559/html
dc.rights.*.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.local.spa.fl_str_mv Acceso abierto
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info:eu-repo/semantics/openAccess
Acceso abierto
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
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eu_rights_str_mv openAccess
dc.format.mimetype.none.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Society for Translational Medicine
dc.publisher.journal.spa.fl_str_mv Translational Lung Cancer Research
institution Universidad El Bosque
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spelling Shi, JinghanYang, FujunZhou, NanfengJiang, YanZhao, YanfengZhu, JunjiePrelaj, ArselaMalhotra, JyotiNormanno, NicolaDanese, ElisaCardona, Andrés F.Hong, XuanJiang, GeningSong, Xiao2021-05-10T17:24:09Z2021-05-10T17:24:09Z2021-032226-4477http://hdl.handle.net/20.500.12495/5848https://doi.org/10.21037/TLCR-21-219instname:Universidad El Bosquereponame:Repositorio Institucional Universidad El Bosquerepourl:https://repositorio.unbosque.edu.coapplication/pdfengSociety for Translational MedicineTranslational Lung Cancer ResearchTranslational Lung Cancer Research, 2226-4477, Vol. 10, Nro. 3, 2021, p. 1444-1456https://tlcr.amegroups.com/article/view/50559/htmlAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Acceso abiertohttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessAcceso abiertoIsochorismatase domain-containing protein 1 (ISOC1) participates in DNA damage repair and inflammation-related pathways to promote lung cancer developmentIsochorismatase domain-containing protein 1 (ISOC1) participates in DNA damage repair and inflammation-related pathways to promote lung cancer developmentArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articlehttp://purl.org/coar/version/c_970fb48d4fbd8a85Isochorismatase domain-containing proteinmiR-4633Lung cancerDNA damage repairInflammationBackground: The advent of novel molecular targets has dramatically changed the treatment landscape of lung cancer in recent years. Isochorismatase domain-containing protein 1 (ISOC1) has been reported as a potential biomarker in gastrointestinal cancer, while its function in lung cancer has not been determined. Methods: The expression levels and prognostic significance of ISOC1 were assessed using bioinformatic analysis. Overexpression of ISOC1 and miR-4633, and knockdown of ISOC1 in non-small cell lung cáncer (NSCLC) cell lines were generated by lentiviral infection with overexpressed or shRNA plasmids. CRISPR/ Cas9 system was applied to knockout ISOC1 in A549 cells. The functions of ISOC1 and miR-4633 in lung cancer development were investigated using cell proliferation, migration, and invasion assays. Xenograft tumor growth assays in nude mice were further assessed the effect of ISOC1 in the tumorigenesis of NSCLC in vivo. Cell cycle distribution analysis was performed to uncover the underlying mechanism of ISOC1 and miR-4633 in promoting NSCLC cell proliferation. Co-immunoprecipitation combined with mass spectrometry and RNA sequencing were performed to uncover the potential mechanism of ISOC1 in lung cancer development. Results: Our results found that ISOC1 expression was upregulated in NSCLC tissues and that increased expression of ISOC1 was significantly associated with worse disease-free survival in NSCLC patients. Overexpression of ISOC1 could increase the proliferation, viability, migration, and invasion of NSCLC cells. Furthermore, miR-4633, located in the first intron of ISOC1, could also promote tumor cell progression and metastasis. Mice xenograft tumor assay showed that knockout of ISOC1 could significantly inhibit tumor growth in vivo. Besides, co-immunoprecipitation combined with mass spectrometry assay revealed that ISOC1 interacted with the proteins of DNA damage repair pathways and that upregulated ISOC1 expression could significantly increase the number of DNA damage lesions. RNA sequencing analysis showed that the downstream signaling pathways mediated by ISOC1 were mainly inflammation-related. Conclusions: We demonstrated that ISOC1 and its intronic miR-4633, both of them could promote NSCLC cell proliferation, migration, invasion, and cell cycle progression. 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