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摘要
The Dickkopf 3 (DKK3) protein antagonizes the Wnt receptor complex in the Wnt signaling pathway; however, to date, there have been no relevant studies investigating its upstream regulatory mechanism in breast cancer (BC), to the best of our knowledge. The present study aimed to explore whether long non-coding RNA MICAL2-1 (lnc-MICAL2-1) sponged microRNA (miR)-25 to regulate DKK3 and inhibit activation of the Wnt/beta-catenin signaling pathway. The Atlas of non-coding RNA in Cancer database was used to measure the expression levels of lnc-MICAL2-1 and their correlation with DKK3 expression levels. In addition, cell proliferation, invasion and migration were determined following the silencing or overexpression of lnc-MICAL2-1. The binding between lnc-MICAL2-1 and miR-25, or miR-25 and DKK3 was verified using RNA pull-down and dual-luciferase reporter assays. The effects of overexpression or knockdown of lnc-MICAL2-1 on DKK3 expression and the Wnt signaling pathway were further evaluated in a nude mouse xenograft model. The results revealed that, compared with in adjacent normal tissue, the expression levels of lnc-MICAL2-1 were downregulated in BC tissues, and the expression levels of lnc-MICAL2-1 were found to be positively correlated with DKK3 expression. The overexpression of lnc-MICAL2-1 in BC cells upregulated the mRNA expression levels of DKK3 and inhibited their proliferation. Results from the RNA pull-down and dual luciferase reporter assays validated that lnc-MICAL2-1 could bind to miR-25, which targets DKK3. The in vivo experimental data demonstrated that lnc-MICAL2-1 inhibited tumor growth via regulating the Wnt signaling pathway. In conclusion, the findings of the present study highlighted a novel molecular mechanism through which lnc-MICAL2-1 may regulate the DKK3-mediated Wnt signaling pathway in BC, highlighting potential targets for the treatment of the disease.
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单位1; 南方医科大学
