miR-125b Promotes Colorectal Cancer Migration and Invasion by Dual-Targeting CFTR and CGN

Metastasis contributes to the poor prognosis of colorectal cancer, the causative factor of which is not fully understood. Previously, we found that miR-125b (Accession number: MIMAT0000423) contributed to cetuximab resistance in colorectal cancer (CRC). In this study, we identified a novel mechanism...

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Autores principales:	Xiaohui Zhang, Tingyu Li, Ya-Nan Han, Minghui Ge, Pei Wang, Lina Sun, Hao Liu, Tianyu Cao, Yongzhan Nie, Daiming Fan, Hao Guo, Kaichun Wu, Xiaodi Zhao, Yuanyuan Lu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	colorectal cancer migration invasion metastasis miRNA Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a75401199bd34e57adcf58a5a717fe88
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spelling	oai:doaj.org-article:a75401199bd34e57adcf58a5a717fe882021-11-25T17:02:57ZmiR-125b Promotes Colorectal Cancer Migration and Invasion by Dual-Targeting CFTR and CGN10.3390/cancers132257102072-6694https://doaj.org/article/a75401199bd34e57adcf58a5a717fe882021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5710https://doaj.org/toc/2072-6694Metastasis contributes to the poor prognosis of colorectal cancer, the causative factor of which is not fully understood. Previously, we found that miR-125b (Accession number: MIMAT0000423) contributed to cetuximab resistance in colorectal cancer (CRC). In this study, we identified a novel mechanism by which miR-125b enhances metastasis by targeting cystic fibrosis transmembrane conductance regulator (CFTR) and the tight junction-associated adaptor cingulin (CGN) in CRC. We found that miR-125b expression was upregulated in primary CRC tumors and metastatic sites compared with adjacent normal tissues. Overexpression of miR-125b in CRC cells enhanced migration capacity, while knockdown of miR-125b decreased migration and invasion. RNA-sequencing (RNA-seq) and dual-luciferase reporter assays identified CFTR and CGN as the target genes of miR-125b, and the inhibitory impact of CFTR and CGN on metastasis was further verified both in vitro and in vivo. Moreover, we found that miR-125b facilitated the epithelial-mesenchymal transition (EMT) process and the expression and secretion of urokinase plasminogen activator (uPA) by targeting CFTR and enhanced the Ras Homolog Family Member A (RhoA)/Rho Kinase (ROCK) pathway activity by targeting CGN. Together, these findings suggest miR-125b as a key functional molecule in CRC and a promising biomarker for the diagnosis and treatment of CRC.Xiaohui ZhangTingyu LiYa-Nan HanMinghui GePei WangLina SunHao LiuTianyu CaoYongzhan NieDaiming FanHao GuoKaichun WuXiaodi ZhaoYuanyuan LuMDPI AGarticlecolorectal cancermigrationinvasionmetastasismiRNANeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5710, p 5710 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colorectal cancer migration invasion metastasis miRNA Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	colorectal cancer migration invasion metastasis miRNA Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Xiaohui Zhang Tingyu Li Ya-Nan Han Minghui Ge Pei Wang Lina Sun Hao Liu Tianyu Cao Yongzhan Nie Daiming Fan Hao Guo Kaichun Wu Xiaodi Zhao Yuanyuan Lu miR-125b Promotes Colorectal Cancer Migration and Invasion by Dual-Targeting CFTR and CGN
description	Metastasis contributes to the poor prognosis of colorectal cancer, the causative factor of which is not fully understood. Previously, we found that miR-125b (Accession number: MIMAT0000423) contributed to cetuximab resistance in colorectal cancer (CRC). In this study, we identified a novel mechanism by which miR-125b enhances metastasis by targeting cystic fibrosis transmembrane conductance regulator (CFTR) and the tight junction-associated adaptor cingulin (CGN) in CRC. We found that miR-125b expression was upregulated in primary CRC tumors and metastatic sites compared with adjacent normal tissues. Overexpression of miR-125b in CRC cells enhanced migration capacity, while knockdown of miR-125b decreased migration and invasion. RNA-sequencing (RNA-seq) and dual-luciferase reporter assays identified CFTR and CGN as the target genes of miR-125b, and the inhibitory impact of CFTR and CGN on metastasis was further verified both in vitro and in vivo. Moreover, we found that miR-125b facilitated the epithelial-mesenchymal transition (EMT) process and the expression and secretion of urokinase plasminogen activator (uPA) by targeting CFTR and enhanced the Ras Homolog Family Member A (RhoA)/Rho Kinase (ROCK) pathway activity by targeting CGN. Together, these findings suggest miR-125b as a key functional molecule in CRC and a promising biomarker for the diagnosis and treatment of CRC.
format	article
author	Xiaohui Zhang Tingyu Li Ya-Nan Han Minghui Ge Pei Wang Lina Sun Hao Liu Tianyu Cao Yongzhan Nie Daiming Fan Hao Guo Kaichun Wu Xiaodi Zhao Yuanyuan Lu
author_facet	Xiaohui Zhang Tingyu Li Ya-Nan Han Minghui Ge Pei Wang Lina Sun Hao Liu Tianyu Cao Yongzhan Nie Daiming Fan Hao Guo Kaichun Wu Xiaodi Zhao Yuanyuan Lu
author_sort	Xiaohui Zhang
title	miR-125b Promotes Colorectal Cancer Migration and Invasion by Dual-Targeting CFTR and CGN
title_short	miR-125b Promotes Colorectal Cancer Migration and Invasion by Dual-Targeting CFTR and CGN
title_full	miR-125b Promotes Colorectal Cancer Migration and Invasion by Dual-Targeting CFTR and CGN
title_fullStr	miR-125b Promotes Colorectal Cancer Migration and Invasion by Dual-Targeting CFTR and CGN
title_full_unstemmed	miR-125b Promotes Colorectal Cancer Migration and Invasion by Dual-Targeting CFTR and CGN
title_sort	mir-125b promotes colorectal cancer migration and invasion by dual-targeting cftr and cgn
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a75401199bd34e57adcf58a5a717fe88
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miR-125b Promotes Colorectal Cancer Migration and Invasion by Dual-Targeting CFTR and CGN

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