MicroRNA-143-3p suppresses tumorigenesis by targeting catenin-δ1 in colorectal cancer

Abstract

Xiaohua Ding,1 Jiying Du,1 Kai Mao,2 Xiaoyu Wang,1 Yuange Ding,1 Fanping Wang1,31School of Inspection and Imaging, Sanquan College of Xinxiang Medical University, 453003, Henan, China; 2Department Two of Thoracic Diseases, Xinxiang Central Hospital, 453003, Henan, China; 3School of Laboratory Medicine, Xinxiang Medical University, 453003, Henan, China Background: Colorectal cancer (CRC) is the third most common malignancy in the United States. Mounting microRNAs (miRNAs) have been identified as oncogenes or tumor suppressors in various cancers including CRC.Materials and methods: The levels of microRNA-143-3p (miR-143-3p) and catenin-δ1 (CTNND1) were determined by RT-qPCR assay. Cell proliferative ability was assessed by Cell Counting Kit-8 assay. Cell migratory and invasive capacities were measured by transwell migration and invasion assay. Luciferase reporter assay was conducted to explore whether miR-143-3p could bind with CTNND1 3'UTR. CTNND1 protein level was determined through Western blot assay. Mouse xenograft models of CRC were established to test the functions and molecular basis of miR-143-3p in the development of CRC in vivo.Results: Low amounts of miR-143-3p were expressed in CRC tissues and cells. Functional analysis revealed that miR-143-3p overexpression suppressed cell proliferation, migration and invasion in CRC. Molecular mechanism exploration indicated that miR-143-3p directly targeted CTNND1. Moreover, enforced expression of CTNND1 contributed to cell proliferation, migration and invasion in CRC, and CTNND1 silencing exerted opposite effects. Restoration experiments disclosed that CTNND1 upregulation weakened the inhibitory effects of miR-143-3p on CRC cell proliferation, migration and invasion. Additionally, miR-143-3p inhibited the growth of HCT116-derived xenograft tumors by targeting CTNND1 in vivo.Conclusion: miR-143-3p hampered the development and progression of CRC by targeting CTNND1 in vitro and in vivo, deepening our understanding of the functions and molecular basis of miR-143-3p in the tumorigenesis of CRC and providing some candidate prognostic markers or therapeutic targets for CRC. Keywords: microRNA-143-3p, CTNND1, colorectal cancer, tumorigenesis

Keywords

• microRNA-143-3p
• CTNND1
• colorectal cancer
• tumorigenesis.