Hsa-miR-425-5p promotes tumor growth and metastasis by activating the CTNND1-mediated β-catenin pathway and EMT in colorectal cancer

被引:35
作者
Liu, Dingsheng [1 ]
Zhang, Hong [1 ]
Cui, Mingming [1 ]
Chen, Chunsheng [1 ]
Feng, Yong [1 ]
机构
[1] China Med Univ, Shengjing Hosp, Dept Gen Surg, Shenyang, Peoples R China
关键词
Colorectal cancer; miR-425-5p; catenin-delta 1 (CTNND1); beta-catenin pathway; tumor growth; metastasis; EPITHELIAL-MESENCHYMAL TRANSITION; CELL MOTILITY; TUMORIGENESIS; PROGRESSION; CATENIN-DELTA-1; FIBRONECTIN;
D O I
10.1080/15384101.2020.1783058
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Colorectal cancer (CRC) is a common malignancy with high mortality. However, the roles of miR-425-5p and its underlying mechanism in CRC remain unknown. Here, RT-qPCR confirmed that miR-425-5p expression was increased by miR-425-5p mimic in SW480 cells and decreased by miR-425-5p inhibitor in LOVO cells. CCK-8, flow cytometry, wound healing and transwell assays revealed that the increased miR-425-5p promoted cell viability, cell cycle entry, migration and invasion in CRC. Besides, miR-425-5p overexpression induced epithelial-mesenchymal transition (EMT) with upregulation of Fibronectin, N-cadherin, Vimentin, and downregulation of E-cadherin. Moreover, miR-425-5p overexpression induced c-myc, Cyclin D1 and MMP7 levels, and promoted beta-catenin translocation to the nucleus. Knockdown of miR-425-5p exerted opposite effects. Luciferase reporter assay indicated that miR-425-5p directly targeted CTNND1. Overexpression of miR-425-5p repressed CTNND1 expression at mRNA and protein levels. Silencing of CTNND1 had the inhibitory effect of miR-425-5p inhibitor on cell proliferation, migration, invasion, EMT, and the activation of beta-catenin signaling pathway. Furthermore, miR-425-5p promoted tumor growth and metastasis in vivo. In conclusion, miR-425-5p may promote tumorigenesis and metastasis through activating CTNND1-mediated beta-catenin pathway, which may provide therapeutic targets for human CRC.
引用
收藏
页码:1917 / 1927
页数:11
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