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Downregulated ARID1A by miR-185 Is Associated With Poor Prognosis and Adverse Outcomes in Colon Adenocarcinoma

AT-rich interaction domain 1A (ARID1A) is a tumor suppressor gene that mutates in several cancer types, including breast cancer, ovarian cancer, and colorectal cancer (CRC). In colon adenocarcinoma (COAD), the low expression of ARID1A was reported but the molecular reason is unclear. We noticed that...

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Autores principales: Baldi, Salem, Khamgan, Hassan, Qian, Yuanyuan, Wu, Han, Zhang, Zhenyu, Zhang, Mengyan, Gao, Yina, Safi, Mohammed, Al-Radhi, Mohammed, Zuo, Yun-Fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367751/
https://www.ncbi.nlm.nih.gov/pubmed/34414106
http://dx.doi.org/10.3389/fonc.2021.679334
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author Baldi, Salem
Khamgan, Hassan
Qian, Yuanyuan
Wu, Han
Zhang, Zhenyu
Zhang, Mengyan
Gao, Yina
Safi, Mohammed
Al-Radhi, Mohammed
Zuo, Yun-Fei
author_facet Baldi, Salem
Khamgan, Hassan
Qian, Yuanyuan
Wu, Han
Zhang, Zhenyu
Zhang, Mengyan
Gao, Yina
Safi, Mohammed
Al-Radhi, Mohammed
Zuo, Yun-Fei
author_sort Baldi, Salem
collection PubMed
description AT-rich interaction domain 1A (ARID1A) is a tumor suppressor gene that mutates in several cancer types, including breast cancer, ovarian cancer, and colorectal cancer (CRC). In colon adenocarcinoma (COAD), the low expression of ARID1A was reported but the molecular reason is unclear. We noticed that ARID1A low expression was associated with increased levels of miR-185 in the COAD. Therefore, this study aims to explore ncRNA-dependent mechanism that regulates ARID1A expression in COAD regarding miR-185. The expression of ARID1A was tested in COAD cell line under the effect of miR-185 mimics compared with inhibitor. The molecular features associated with loss of ARID1A and its association with tumor prognosis were analyzed using multi-platform data from The Cancer Genome Atlas (TCGA), and gene set enrichment analysis (GSEA) to identify potential signaling pathways associated with ARID1A alterations in colon cancer. Kaplan-Meier survival curve showed that a low level of ARID1A was closely related to low survival rate in patients with COAD. Results showed that inhibiting miR-185 expression in the COAD cell line significantly restored the expression of ARID1A. Further, the increased expression of ARID1A significantly improved the prolonged overall survival of COAD. We noticed that there is a possible relationship between ARID1A high expression and tumor microenvironment infiltrating immune cells. Furthermore, the increase of ARID1A in tumor cells enhanced the response of inflammatory chemokines. In conclusion, this study demonstrates that ARID1A is a direct target of miR-185 in COAD that regulates the immune modulations in the microenvironment of COAD.
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spelling pubmed-83677512021-08-18 Downregulated ARID1A by miR-185 Is Associated With Poor Prognosis and Adverse Outcomes in Colon Adenocarcinoma Baldi, Salem Khamgan, Hassan Qian, Yuanyuan Wu, Han Zhang, Zhenyu Zhang, Mengyan Gao, Yina Safi, Mohammed Al-Radhi, Mohammed Zuo, Yun-Fei Front Oncol Oncology AT-rich interaction domain 1A (ARID1A) is a tumor suppressor gene that mutates in several cancer types, including breast cancer, ovarian cancer, and colorectal cancer (CRC). In colon adenocarcinoma (COAD), the low expression of ARID1A was reported but the molecular reason is unclear. We noticed that ARID1A low expression was associated with increased levels of miR-185 in the COAD. Therefore, this study aims to explore ncRNA-dependent mechanism that regulates ARID1A expression in COAD regarding miR-185. The expression of ARID1A was tested in COAD cell line under the effect of miR-185 mimics compared with inhibitor. The molecular features associated with loss of ARID1A and its association with tumor prognosis were analyzed using multi-platform data from The Cancer Genome Atlas (TCGA), and gene set enrichment analysis (GSEA) to identify potential signaling pathways associated with ARID1A alterations in colon cancer. Kaplan-Meier survival curve showed that a low level of ARID1A was closely related to low survival rate in patients with COAD. Results showed that inhibiting miR-185 expression in the COAD cell line significantly restored the expression of ARID1A. Further, the increased expression of ARID1A significantly improved the prolonged overall survival of COAD. We noticed that there is a possible relationship between ARID1A high expression and tumor microenvironment infiltrating immune cells. Furthermore, the increase of ARID1A in tumor cells enhanced the response of inflammatory chemokines. In conclusion, this study demonstrates that ARID1A is a direct target of miR-185 in COAD that regulates the immune modulations in the microenvironment of COAD. Frontiers Media S.A. 2021-08-02 /pmc/articles/PMC8367751/ /pubmed/34414106 http://dx.doi.org/10.3389/fonc.2021.679334 Text en Copyright © 2021 Baldi, Khamgan, Qian, Wu, Zhang, Zhang, Gao, Safi, Al-Radhi and Zuo https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Baldi, Salem
Khamgan, Hassan
Qian, Yuanyuan
Wu, Han
Zhang, Zhenyu
Zhang, Mengyan
Gao, Yina
Safi, Mohammed
Al-Radhi, Mohammed
Zuo, Yun-Fei
Downregulated ARID1A by miR-185 Is Associated With Poor Prognosis and Adverse Outcomes in Colon Adenocarcinoma
title Downregulated ARID1A by miR-185 Is Associated With Poor Prognosis and Adverse Outcomes in Colon Adenocarcinoma
title_full Downregulated ARID1A by miR-185 Is Associated With Poor Prognosis and Adverse Outcomes in Colon Adenocarcinoma
title_fullStr Downregulated ARID1A by miR-185 Is Associated With Poor Prognosis and Adverse Outcomes in Colon Adenocarcinoma
title_full_unstemmed Downregulated ARID1A by miR-185 Is Associated With Poor Prognosis and Adverse Outcomes in Colon Adenocarcinoma
title_short Downregulated ARID1A by miR-185 Is Associated With Poor Prognosis and Adverse Outcomes in Colon Adenocarcinoma
title_sort downregulated arid1a by mir-185 is associated with poor prognosis and adverse outcomes in colon adenocarcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367751/
https://www.ncbi.nlm.nih.gov/pubmed/34414106
http://dx.doi.org/10.3389/fonc.2021.679334
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