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

Abstract
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.
AuthorsXiaohui 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
JournalCancers (Cancers (Basel)) Vol. 13 Issue 22 (Nov 15 2021) ISSN: 2072-6694 [Print] Switzerland
PMID34830864 (Publication Type: Journal Article)

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