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Abstract

Several studies have demonstrated the dysregulation of miR-449b-5p in numerous types of human cancers. However, the understanding of the function of miR-449b-5p the mechanisms linking its expression to the development of colorectal cancer (CRC) remains limited. The current work documented the decrease in the level of miR-449b-5p in CRC tissues as well as in CRC-derived cell lines. Functional assays indicated that the overexpression of miR-449b-5p inhibits proliferation, migration, and invasion of CRC cells. Mechanistically, the direct target of miR-449b-5p in CRC cells was identified as the catenin delta 1 (CTNND1) protein. Increased level of miR-449b-5p in CRC cells downregulated β-catenin, WNT11, cyclin D1, and MMP7. Conversely, the restoration of CTNND1 expression abrogated the inactivation of Wnt/β-catenin signaling induced by miR-449b-5p. In conclusion, the present investigation demonstrates for the first time that miR-449b-5p is capable of inhibiting the progression of CRC. This effect is achieved, at least in part, by targeting CTNND1-mediated Wnt/β-catenin signaling. The accumulated data point to miR-449b-5p as a novel target in the treatment of CRC.

Keywords: miR-449b-5p; Colorectal cancer; CTNND1; Wnt/β- catenin signaling; Tumor growth and metastasis