miRNA-200c-3p deficiency promotes epithelial-mesenchymal transition in triple-negative breast cancer by activating CRKL expression

Abstract

Abstract Epithelial-mesenchymal transition (EMT) plays an important role in malignant progression of Triple-negative breast cancer (TNBC). Many studies have confirmed that miRNA-200c-3p is related to EMT. And we found that it is involved in the regulation of EMT, but the exact mechanism is unclear. CRKL is highly expressed in a variety of tumors and plays a role in EMT. In this study, the potential targets of miRNA-200c-3p were searched in miRPathDB, Targetscan and PicTar. And there are 68 potential targets at the intersection of the three databases. Then, bioinformatics and text mining performed by Coremine Medica, and found that among 68 potential targets, CRKL has the strongest correlation with EMT in TNBC. Therefore, we speculated that miRNA-200c-3p involvement in EMT might be related to CRKL. To verify miRNA-200c-3p inhibits the malignant phenotype of TNBC by regulating CRKL, RT‒PCR, western blotting, Clonal formation assays,CCK-8 proliferation assays, transwell invasion assays, Luciferase reporter assay and nude mouse transplantation tumor assay were performed. In this study, we found that miRNA-200c-3p is under-expressed and EMT-related genes are up-regulated in TNBC, and miRNA-200c-3p can inhibit cancer cell proliferation, invasion and the expression of EMT-related genes and proteins in TNBC. Further research confirmed that miRNA-200c-3p could inhibit EMT by inhibiting the expression of CRKL that directly combining CRKL gene.

Keywords

• Malignant phenotype
• Epithelial-mesenchymal transition
• Triple-negative breast cancer
• CRKL