CircIMMP2L promotes esophageal squamous cell carcinoma malignant progression via CtBP1 nuclear retention dependent epigenetic modification

Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers. The two major lethal causes of ESCC are diagnosis at an advanced stage and lymph node metastasis (LNM). Circular RNAs (circRNAs) play critical regulatory roles in cancer progression, though, largely...

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Autores principales:	Yingkuan Liang, Qixing Mao, Lin Wang, Wenjie Xia, Bing Chen, Hui Wang, Rutao Li, Lin Xu, Feng Jiang, Gaochao Dong
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	circIMMP2L circRNA ESCC CtBP1 HDAC1 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b69c7cc996564f908c69951c0705cc03
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spelling	oai:doaj.org-article:b69c7cc996564f908c69951c0705cc032021-11-11T12:06:40ZCircIMMP2L promotes esophageal squamous cell carcinoma malignant progression via CtBP1 nuclear retention dependent epigenetic modification2001-132610.1002/ctm2.519https://doaj.org/article/b69c7cc996564f908c69951c0705cc032021-09-01T00:00:00Zhttps://doi.org/10.1002/ctm2.519https://doaj.org/toc/2001-1326Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers. The two major lethal causes of ESCC are diagnosis at an advanced stage and lymph node metastasis (LNM). Circular RNAs (circRNAs) play critical regulatory roles in cancer progression, though, largely through unclear mechanisms. However, the character of circRNAs in the malignant progression of ESCC remains unclear. Methods The circRNA microarray was used to explore the circRNAs that were differentially expressed between ESCC and paired adjacent normal tissues. The function of circIMMP2L was validated by gain or loss of function assays. Pull‐down, RNA immunoprecipitation assays were used to demonstrate the biological mechanism of circIMMP2L. Tissue microarray (TMA), specimen, and paired plasma were investigated to evaluate the clinical significance of circIMMP2L. Results CircIMMP2L, commonly upregulated in tumor and plasma from advanced‐stage ESCC patients and LNM patients, predicts poorer patient survival. CircIMMP2L was also found to be a significant indicator for LNM, even in the T1 stage of ESCC. CircIMMP2L depletion suppressed the malignant progression of ESCC both in vitro and in vivo. Mechanistically, cytoplasmic circIMMP2L interacted with CtBP1 and facilitated the nuclear retention of CtBP1 in a CtBP2‐independent manner. Moreover, circIMMP2L promoted the interaction of CtBP1 with HDAC1 in the nucleus, which is essential for epigenetic remodeling and transcriptional suppression of E‐cadherin and p21. Conclusions These findings demonstrated that circIMMP2L promotes the malignant progression of ESCC mediated by CtBP1 nuclear retention and is a robust biomarker for the diagnosis, prognosis, and LNM in ESCC. Further, the findings extend our knowledge about the mechanism of circRNA regulation of gene transcription through epigenetics.Yingkuan LiangQixing MaoLin WangWenjie XiaBing ChenHui WangRutao LiLin XuFeng JiangGaochao DongWileyarticlecircIMMP2LcircRNAESCCCtBP1HDAC1Medicine (General)R5-920ENClinical and Translational Medicine, Vol 11, Iss 9, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	circIMMP2L circRNA ESCC CtBP1 HDAC1 Medicine (General) R5-920
spellingShingle	circIMMP2L circRNA ESCC CtBP1 HDAC1 Medicine (General) R5-920 Yingkuan Liang Qixing Mao Lin Wang Wenjie Xia Bing Chen Hui Wang Rutao Li Lin Xu Feng Jiang Gaochao Dong CircIMMP2L promotes esophageal squamous cell carcinoma malignant progression via CtBP1 nuclear retention dependent epigenetic modification
description	Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers. The two major lethal causes of ESCC are diagnosis at an advanced stage and lymph node metastasis (LNM). Circular RNAs (circRNAs) play critical regulatory roles in cancer progression, though, largely through unclear mechanisms. However, the character of circRNAs in the malignant progression of ESCC remains unclear. Methods The circRNA microarray was used to explore the circRNAs that were differentially expressed between ESCC and paired adjacent normal tissues. The function of circIMMP2L was validated by gain or loss of function assays. Pull‐down, RNA immunoprecipitation assays were used to demonstrate the biological mechanism of circIMMP2L. Tissue microarray (TMA), specimen, and paired plasma were investigated to evaluate the clinical significance of circIMMP2L. Results CircIMMP2L, commonly upregulated in tumor and plasma from advanced‐stage ESCC patients and LNM patients, predicts poorer patient survival. CircIMMP2L was also found to be a significant indicator for LNM, even in the T1 stage of ESCC. CircIMMP2L depletion suppressed the malignant progression of ESCC both in vitro and in vivo. Mechanistically, cytoplasmic circIMMP2L interacted with CtBP1 and facilitated the nuclear retention of CtBP1 in a CtBP2‐independent manner. Moreover, circIMMP2L promoted the interaction of CtBP1 with HDAC1 in the nucleus, which is essential for epigenetic remodeling and transcriptional suppression of E‐cadherin and p21. Conclusions These findings demonstrated that circIMMP2L promotes the malignant progression of ESCC mediated by CtBP1 nuclear retention and is a robust biomarker for the diagnosis, prognosis, and LNM in ESCC. Further, the findings extend our knowledge about the mechanism of circRNA regulation of gene transcription through epigenetics.
format	article
author	Yingkuan Liang Qixing Mao Lin Wang Wenjie Xia Bing Chen Hui Wang Rutao Li Lin Xu Feng Jiang Gaochao Dong
author_facet	Yingkuan Liang Qixing Mao Lin Wang Wenjie Xia Bing Chen Hui Wang Rutao Li Lin Xu Feng Jiang Gaochao Dong
author_sort	Yingkuan Liang
title	CircIMMP2L promotes esophageal squamous cell carcinoma malignant progression via CtBP1 nuclear retention dependent epigenetic modification
title_short	CircIMMP2L promotes esophageal squamous cell carcinoma malignant progression via CtBP1 nuclear retention dependent epigenetic modification
title_full	CircIMMP2L promotes esophageal squamous cell carcinoma malignant progression via CtBP1 nuclear retention dependent epigenetic modification
title_fullStr	CircIMMP2L promotes esophageal squamous cell carcinoma malignant progression via CtBP1 nuclear retention dependent epigenetic modification
title_full_unstemmed	CircIMMP2L promotes esophageal squamous cell carcinoma malignant progression via CtBP1 nuclear retention dependent epigenetic modification
title_sort	circimmp2l promotes esophageal squamous cell carcinoma malignant progression via ctbp1 nuclear retention dependent epigenetic modification
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/b69c7cc996564f908c69951c0705cc03
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_version_	1718439069286924288

CircIMMP2L promotes esophageal squamous cell carcinoma malignant progression via CtBP1 nuclear retention dependent epigenetic modification

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