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circEZH2(E2) (/E3 ) is a dual suppressor of miR363/miR708 to promote EZH2 expression and prostate cancer progression

The histone methyltransferase enhancer of zeste homolog 2 (EZH2) is overexpressed in a variety of malignancies including prostate cancer (PCa) and may play important roles in tumor progression. Gene copy number gains, enhanced transcription, and a few circRNAs have been reported to upregulate EZH2....

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Autores principales: Su, Zhengzheng, Zhang, Mengni, Luo, Han, Zhong, Jinjing, Tan, Junya, Xu, Yunyi, Pan, Xiuyi, Zeng, Hao, Nie, Ling, Xu, Miao, Chen, Ni, Chen, Xueqin, Zhou, Qiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067432/
https://www.ncbi.nlm.nih.gov/pubmed/36519785
http://dx.doi.org/10.1111/cas.15694
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author Su, Zhengzheng
Zhang, Mengni
Luo, Han
Zhong, Jinjing
Tan, Junya
Xu, Yunyi
Pan, Xiuyi
Zeng, Hao
Nie, Ling
Xu, Miao
Chen, Ni
Chen, Xueqin
Zhou, Qiao
author_facet Su, Zhengzheng
Zhang, Mengni
Luo, Han
Zhong, Jinjing
Tan, Junya
Xu, Yunyi
Pan, Xiuyi
Zeng, Hao
Nie, Ling
Xu, Miao
Chen, Ni
Chen, Xueqin
Zhou, Qiao
author_sort Su, Zhengzheng
collection PubMed
description The histone methyltransferase enhancer of zeste homolog 2 (EZH2) is overexpressed in a variety of malignancies including prostate cancer (PCa) and may play important roles in tumor progression. Gene copy number gains, enhanced transcription, and a few circRNAs have been reported to upregulate EZH2. It was not known whether EZH2 itself generates circRNAs that promote its own expression. We here report the identification of circEZH2(E2/E3) that is derived from exons 2 and 3 of the EZH2 gene and overexpressed in PCa. We show that circEZH2(E2/E3) functions as a dual inhibitor for both miR363 and miR708 that target the EZH2 3′UTR and CDS, respectively, resulting in the upregulation of EZH2 expression and hence the downregulation of EZH2‐repressed genes (e.g., CDH1 and DAB2IP), and enhancement of PCa cell proliferation, migration, invasion, and xenograft PCa growth. Overexpression of circEZH2(E2/E3) is significantly correlated with higher tumor grade, tumor progression, and unfavorable progression‐free and disease‐specific survival in PCa patients. These findings show a novel autoenhancing EZH2–circEZH2(E2/E3)‐miR363/miR708–EZH2 regulatory loop, by which circEZH2(E2/E3) plays important roles in PCa tumorigenesis and progression by upregulating EZH2, and may have potential diagnostic, prognostic, and therapeutic uses in PCa management.
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spelling pubmed-100674322023-04-04 circEZH2(E2) (/E3 ) is a dual suppressor of miR363/miR708 to promote EZH2 expression and prostate cancer progression Su, Zhengzheng Zhang, Mengni Luo, Han Zhong, Jinjing Tan, Junya Xu, Yunyi Pan, Xiuyi Zeng, Hao Nie, Ling Xu, Miao Chen, Ni Chen, Xueqin Zhou, Qiao Cancer Sci Original Articles The histone methyltransferase enhancer of zeste homolog 2 (EZH2) is overexpressed in a variety of malignancies including prostate cancer (PCa) and may play important roles in tumor progression. Gene copy number gains, enhanced transcription, and a few circRNAs have been reported to upregulate EZH2. It was not known whether EZH2 itself generates circRNAs that promote its own expression. We here report the identification of circEZH2(E2/E3) that is derived from exons 2 and 3 of the EZH2 gene and overexpressed in PCa. We show that circEZH2(E2/E3) functions as a dual inhibitor for both miR363 and miR708 that target the EZH2 3′UTR and CDS, respectively, resulting in the upregulation of EZH2 expression and hence the downregulation of EZH2‐repressed genes (e.g., CDH1 and DAB2IP), and enhancement of PCa cell proliferation, migration, invasion, and xenograft PCa growth. Overexpression of circEZH2(E2/E3) is significantly correlated with higher tumor grade, tumor progression, and unfavorable progression‐free and disease‐specific survival in PCa patients. These findings show a novel autoenhancing EZH2–circEZH2(E2/E3)‐miR363/miR708–EZH2 regulatory loop, by which circEZH2(E2/E3) plays important roles in PCa tumorigenesis and progression by upregulating EZH2, and may have potential diagnostic, prognostic, and therapeutic uses in PCa management. John Wiley and Sons Inc. 2022-12-28 /pmc/articles/PMC10067432/ /pubmed/36519785 http://dx.doi.org/10.1111/cas.15694 Text en © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Su, Zhengzheng
Zhang, Mengni
Luo, Han
Zhong, Jinjing
Tan, Junya
Xu, Yunyi
Pan, Xiuyi
Zeng, Hao
Nie, Ling
Xu, Miao
Chen, Ni
Chen, Xueqin
Zhou, Qiao
circEZH2(E2) (/E3 ) is a dual suppressor of miR363/miR708 to promote EZH2 expression and prostate cancer progression
title circEZH2(E2) (/E3 ) is a dual suppressor of miR363/miR708 to promote EZH2 expression and prostate cancer progression
title_full circEZH2(E2) (/E3 ) is a dual suppressor of miR363/miR708 to promote EZH2 expression and prostate cancer progression
title_fullStr circEZH2(E2) (/E3 ) is a dual suppressor of miR363/miR708 to promote EZH2 expression and prostate cancer progression
title_full_unstemmed circEZH2(E2) (/E3 ) is a dual suppressor of miR363/miR708 to promote EZH2 expression and prostate cancer progression
title_short circEZH2(E2) (/E3 ) is a dual suppressor of miR363/miR708 to promote EZH2 expression and prostate cancer progression
title_sort circezh2(e2) (/e3 ) is a dual suppressor of mir363/mir708 to promote ezh2 expression and prostate cancer progression
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067432/
https://www.ncbi.nlm.nih.gov/pubmed/36519785
http://dx.doi.org/10.1111/cas.15694
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