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.