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...
- 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
- 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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|
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 |
dc.type.coar.none.fl_str_mv |
http://purl.org/coar/resource_type/c_6501 |
dc.type.driver.none.fl_str_mv |
info:eu-repo/semantics/article |
format |
http://purl.org/coar/resource_type/c_6501 |
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 |
dc.identifier.repourl.none.fl_str_mv |
repourl:https://repositorio.unbosque.edu.co |
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 |
dc.rights.accessrights.none.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 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/ Acceso abierto http://purl.org/coar/access_right/c_abf2 |
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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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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