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CircESRP1 inhibits clear cell renal cell carcinoma progression through the CTCF-mediated positive feedback loop

Circular RNA (circRNA), a closed continuous loop formed by back-splicing, has been confirmed to be implicated in a variety of human diseases including cancers. However, the underlying molecular mechanism of circRNA regulating the progression of renal cell carcinoma (RCC) remains largely unclear. In...

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Autores principales: Gong, Lin-Jing, Wang, Xin-Yuan, Yao, Xu-dong, Wu, Xu, Gu, Wen-Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590696/
https://www.ncbi.nlm.nih.gov/pubmed/34775467
http://dx.doi.org/10.1038/s41419-021-04366-4
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author Gong, Lin-Jing
Wang, Xin-Yuan
Yao, Xu-dong
Wu, Xu
Gu, Wen-Yu
author_facet Gong, Lin-Jing
Wang, Xin-Yuan
Yao, Xu-dong
Wu, Xu
Gu, Wen-Yu
author_sort Gong, Lin-Jing
collection PubMed
description Circular RNA (circRNA), a closed continuous loop formed by back-splicing, has been confirmed to be implicated in a variety of human diseases including cancers. However, the underlying molecular mechanism of circRNA regulating the progression of renal cell carcinoma (RCC) remains largely unclear. In the present study, we identified a novel circular RNA, circESRP1, that derived from the ESRP1 gene locus at 8q22.1 exons. Lower expression of circESRP1 was found in clear cell RCC (ccRCC) tissues and cell lines. Besides, circESRP1 expression level showed inversely correlated with the advanced tumor size, TNM stage and distant metastasis of ccRCC. The expression level of circESRP1 exhibited a positive correlation with CTCF protein but negatively correlated with miR-3942 in 79 ccRCC tissues. In vivo experiments, we found that overexpression of circESRP1 effectively repressed xenograft tumor growth and inhibited c-Myc-mediated EMT progression. CircESRP1 acted as a sponge to competitively bind with miR-3942 as confirmed through RNA pull-down, RIP and dual-luciferase reporter assays. Moreover, CTCF, a downstream target of miR-3942, was validated to specifically promote the circESRP1 transcript expression and regulated by circESRP1/miR-3942 pathway to form a positive feedback loop. We also revealed that the circESRP1/miR-3942/CTCF feedback loop regulated the ccRCC cell functions via c-Myc mediated EMT process. This study provides a novel regulatory model of circRNA via forming a positive-feedback loop that perpetuates the circESRP1/miR-3942/CTCF axis, suggesting that this signaling may serve as a novel target for the treatment of ccRCC.
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spelling pubmed-85906962021-11-17 CircESRP1 inhibits clear cell renal cell carcinoma progression through the CTCF-mediated positive feedback loop Gong, Lin-Jing Wang, Xin-Yuan Yao, Xu-dong Wu, Xu Gu, Wen-Yu Cell Death Dis Article Circular RNA (circRNA), a closed continuous loop formed by back-splicing, has been confirmed to be implicated in a variety of human diseases including cancers. However, the underlying molecular mechanism of circRNA regulating the progression of renal cell carcinoma (RCC) remains largely unclear. In the present study, we identified a novel circular RNA, circESRP1, that derived from the ESRP1 gene locus at 8q22.1 exons. Lower expression of circESRP1 was found in clear cell RCC (ccRCC) tissues and cell lines. Besides, circESRP1 expression level showed inversely correlated with the advanced tumor size, TNM stage and distant metastasis of ccRCC. The expression level of circESRP1 exhibited a positive correlation with CTCF protein but negatively correlated with miR-3942 in 79 ccRCC tissues. In vivo experiments, we found that overexpression of circESRP1 effectively repressed xenograft tumor growth and inhibited c-Myc-mediated EMT progression. CircESRP1 acted as a sponge to competitively bind with miR-3942 as confirmed through RNA pull-down, RIP and dual-luciferase reporter assays. Moreover, CTCF, a downstream target of miR-3942, was validated to specifically promote the circESRP1 transcript expression and regulated by circESRP1/miR-3942 pathway to form a positive feedback loop. We also revealed that the circESRP1/miR-3942/CTCF feedback loop regulated the ccRCC cell functions via c-Myc mediated EMT process. This study provides a novel regulatory model of circRNA via forming a positive-feedback loop that perpetuates the circESRP1/miR-3942/CTCF axis, suggesting that this signaling may serve as a novel target for the treatment of ccRCC. Nature Publishing Group UK 2021-11-13 /pmc/articles/PMC8590696/ /pubmed/34775467 http://dx.doi.org/10.1038/s41419-021-04366-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Gong, Lin-Jing
Wang, Xin-Yuan
Yao, Xu-dong
Wu, Xu
Gu, Wen-Yu
CircESRP1 inhibits clear cell renal cell carcinoma progression through the CTCF-mediated positive feedback loop
title CircESRP1 inhibits clear cell renal cell carcinoma progression through the CTCF-mediated positive feedback loop
title_full CircESRP1 inhibits clear cell renal cell carcinoma progression through the CTCF-mediated positive feedback loop
title_fullStr CircESRP1 inhibits clear cell renal cell carcinoma progression through the CTCF-mediated positive feedback loop
title_full_unstemmed CircESRP1 inhibits clear cell renal cell carcinoma progression through the CTCF-mediated positive feedback loop
title_short CircESRP1 inhibits clear cell renal cell carcinoma progression through the CTCF-mediated positive feedback loop
title_sort circesrp1 inhibits clear cell renal cell carcinoma progression through the ctcf-mediated positive feedback loop
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590696/
https://www.ncbi.nlm.nih.gov/pubmed/34775467
http://dx.doi.org/10.1038/s41419-021-04366-4
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