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

Abstract 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 unc...

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Autores principales:	Lin-Jing Gong, Xin-Yuan Wang, Xu-dong Yao, Xu Wu, Wen-Yu Gu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/c31189dbdd2a4a248bec5ec8e1ed07d0
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spelling	oai:doaj.org-article:c31189dbdd2a4a248bec5ec8e1ed07d02021-11-14T12:06:37ZCircESRP1 inhibits clear cell renal cell carcinoma progression through the CTCF-mediated positive feedback loop10.1038/s41419-021-04366-42041-4889https://doaj.org/article/c31189dbdd2a4a248bec5ec8e1ed07d02021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04366-4https://doaj.org/toc/2041-4889Abstract 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.Lin-Jing GongXin-Yuan WangXu-dong YaoXu WuWen-Yu GuNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 11, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Lin-Jing Gong Xin-Yuan Wang Xu-dong Yao Xu Wu Wen-Yu Gu CircESRP1 inhibits clear cell renal cell carcinoma progression through the CTCF-mediated positive feedback loop
description	Abstract 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.
format	article
author	Lin-Jing Gong Xin-Yuan Wang Xu-dong Yao Xu Wu Wen-Yu Gu
author_facet	Lin-Jing Gong Xin-Yuan Wang Xu-dong Yao Xu Wu Wen-Yu Gu
author_sort	Lin-Jing Gong
title	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_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_sort	circesrp1 inhibits clear cell renal cell carcinoma progression through the ctcf-mediated positive feedback loop
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/c31189dbdd2a4a248bec5ec8e1ed07d0
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CircESRP1 inhibits clear cell renal cell carcinoma progression through the CTCF-mediated positive feedback loop

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