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Interferon-stimulated gene 15 promotes progression of endometrial carcinoma and weakens antitumor immune response

Endometrial carcinoma (EC) is one of the most common gynecological cancers with a poor prognosis. Therefore, clarifying the details of the molecular mechanisms is of great importance for EC diagnosis and clinical management. Interferon-stimulated gene 15 (ISG15) plays an important role in the develo...

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Autores principales: Zhao, Xiwa, Wang, Jingjing, Wang, Yaojie, Zhang, Mengmeng, Zhao, Wei, Zhang, Hui, Zhao, Lianmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9073416/
https://www.ncbi.nlm.nih.gov/pubmed/35445736
http://dx.doi.org/10.3892/or.2022.8321
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author Zhao, Xiwa
Wang, Jingjing
Wang, Yaojie
Zhang, Mengmeng
Zhao, Wei
Zhang, Hui
Zhao, Lianmei
author_facet Zhao, Xiwa
Wang, Jingjing
Wang, Yaojie
Zhang, Mengmeng
Zhao, Wei
Zhang, Hui
Zhao, Lianmei
author_sort Zhao, Xiwa
collection PubMed
description Endometrial carcinoma (EC) is one of the most common gynecological cancers with a poor prognosis. Therefore, clarifying the details of the molecular mechanisms is of great importance for EC diagnosis and clinical management. Interferon-stimulated gene 15 (ISG15) plays an important role in the development of various cancers. However, its role in EC remains unclear. High ISG15 expression was observed in EC, which was associated with poor clinical outcomes and pathological stage of patients with EC, thus representing a promising marker for EC progression. Further exploratory analysis revealed that the elevated ISG15 levels in EC were driven by aberrant DNA methylation, independent of copy number variation and specific transcription factor aberrations. Accordingly, knockdown of ISG15 by small interfering RNA attenuated the malignant cellular phenotype of EC cell lines, including proliferation and colony formation in vitro. Finally, investigation of the molecular mechanisms indicated that ISG15 promoted the cell cycle G1/S transition in EC. Furthermore, ISG15 promoted EC progression by activating the MYC proto-oncogene protein signaling pathway. Moreover, ECs with high levels of ISG15 harbored a more vital immune escape ability, evidenced not only by significantly less invasive CD8(+) T cells, but also higher expression of T cell inhibitory factors, such as programmed death-ligand 1. These results suggest a tumor-promoting role of ISG15 in EC, which may be a promising marker for diagnosis, prognosis and therapeutic immunity.
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spelling pubmed-90734162022-05-07 Interferon-stimulated gene 15 promotes progression of endometrial carcinoma and weakens antitumor immune response Zhao, Xiwa Wang, Jingjing Wang, Yaojie Zhang, Mengmeng Zhao, Wei Zhang, Hui Zhao, Lianmei Oncol Rep Articles Endometrial carcinoma (EC) is one of the most common gynecological cancers with a poor prognosis. Therefore, clarifying the details of the molecular mechanisms is of great importance for EC diagnosis and clinical management. Interferon-stimulated gene 15 (ISG15) plays an important role in the development of various cancers. However, its role in EC remains unclear. High ISG15 expression was observed in EC, which was associated with poor clinical outcomes and pathological stage of patients with EC, thus representing a promising marker for EC progression. Further exploratory analysis revealed that the elevated ISG15 levels in EC were driven by aberrant DNA methylation, independent of copy number variation and specific transcription factor aberrations. Accordingly, knockdown of ISG15 by small interfering RNA attenuated the malignant cellular phenotype of EC cell lines, including proliferation and colony formation in vitro. Finally, investigation of the molecular mechanisms indicated that ISG15 promoted the cell cycle G1/S transition in EC. Furthermore, ISG15 promoted EC progression by activating the MYC proto-oncogene protein signaling pathway. Moreover, ECs with high levels of ISG15 harbored a more vital immune escape ability, evidenced not only by significantly less invasive CD8(+) T cells, but also higher expression of T cell inhibitory factors, such as programmed death-ligand 1. These results suggest a tumor-promoting role of ISG15 in EC, which may be a promising marker for diagnosis, prognosis and therapeutic immunity. D.A. Spandidos 2022-06 2022-04-21 /pmc/articles/PMC9073416/ /pubmed/35445736 http://dx.doi.org/10.3892/or.2022.8321 Text en Copyright: © Zhao et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zhao, Xiwa
Wang, Jingjing
Wang, Yaojie
Zhang, Mengmeng
Zhao, Wei
Zhang, Hui
Zhao, Lianmei
Interferon-stimulated gene 15 promotes progression of endometrial carcinoma and weakens antitumor immune response
title Interferon-stimulated gene 15 promotes progression of endometrial carcinoma and weakens antitumor immune response
title_full Interferon-stimulated gene 15 promotes progression of endometrial carcinoma and weakens antitumor immune response
title_fullStr Interferon-stimulated gene 15 promotes progression of endometrial carcinoma and weakens antitumor immune response
title_full_unstemmed Interferon-stimulated gene 15 promotes progression of endometrial carcinoma and weakens antitumor immune response
title_short Interferon-stimulated gene 15 promotes progression of endometrial carcinoma and weakens antitumor immune response
title_sort interferon-stimulated gene 15 promotes progression of endometrial carcinoma and weakens antitumor immune response
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9073416/
https://www.ncbi.nlm.nih.gov/pubmed/35445736
http://dx.doi.org/10.3892/or.2022.8321
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