miR-576-5p promotes epithelial-to-mesenchymal transition in colorectal cancer by targeting the Wnt5a-mediated Wnt/β-catenin signaling pathway

Colorectal cancer (CRC) is one of the most common types of malignancy and the third most commonly diagnosed form of cancer worldwide, ranking as the fourth leading cause of cancer-associated mortality. MicroRNA (miR)-576-5p has been reported to be highly expressed in patients with CRC; however, its biological role remains unclear. The present study aimed therefore to investigate the biological role and underlying mechanism of miR-576-5p in CRC cell line SW480. The viability of SW480 cells following transfection with miR-576-5p mimic or inhibitor was analyzed using MTT assay. Wound healing and Transwell assays were performed to determine the cell migratory and invasive abilities, respectively. A dual luciferase reporter assay was used to verify the predicted binding site between miR-576-5p and Wnt5a. Reverse transcription-quantitative PCR and western blotting were used to analyze the expression levels of miR-576-5p, E-cadherin, N-cadherin, vimentin, Snail1, Wnt5a, beta-catenin, c-myc, cyclin D1 and p/t-c-Jun. Using bioinformatics analysis, high expression of miR-576-5p was found not only in tumor tissues, compared with the normal tissue, but also in CRC cells, compared with NCM460 cells. Furthermore, the inhibition of miR-576-5p expression significantly decreased the cell viability and the migratory and invasive abilities of SW480 cells, and suppressed the epithelial-to-mesenchymal transition (EMT). In addition, miR-576-5p could interact with Wnt5a and regulate the expression level of Wnt5a in order to influence the activity of Wnt/beta-catenin signaling. The results from rescue experiments further demonstrated that the effect of miR-576-5p overexpression on cell metastasis and EMT was reversed by Wnt5a overexpression or treatment with XAV-939, which is an inhibitor of the Wnt/beta-catenin signaling pathway. In conclusion, the findings from the present study suggested that inhibition of miR-576-5p may suppress SW480 cell metastasis and EMT by targeting Wnt5a and regulating the Wnt5a-mediated Wnt/beta-catenin signaling pathway, providing a potential therapeutic target for the treatment of CRC.

Automated summary

The study reveals that high expression of miR-576-5p is common in colorectal cancer tissues and cells, influencing the viability and migratory abilities of SW480 cells through regulating the Wnt5a-mediated Wnt/beta-catenin signaling pathway, suppressing epithelial-to-mesenchymal transition (EMT).