摘要
Cancer stem cells (CSCs) are involved in tumorigenesis, tumour recurrence and therapy resistance and Wnt signalling is essential for the development of the biological traits of CSCs. In non-small cell lung carcinoma (NSCLC), unlike in colon cancer, mutations in beta-catenin and APC genes are uncommon; thus, the mechanism underlying the constitutive activation of Wnt signalling in NSCLC remains unclear. Here we report that miR-582-3p expression correlates with the overall-and recurrence-free-survival of NSCLC patients, and miR-582-3p has an activating effect on Wnt/beta-catenin signalling. miR-582-3p overexpression simultaneously targets multiple negative regulators of the Wnt/b-catenin pathway, namely, AXIN2, DKK3 and SFRP1. Consequently, miR-582-3p promotes CSC traits of NSCLC cells in vitro and tumorigenesis and tumour recurrence in vivo. Antagonizing miR-582-3p potently inhibits tumour initiation and progression in xenografted animal models. These findings suggest that miR-582-3p mediates the constitutive activation of Wnt/b-catenin signalling, likely serving as a potential therapeutic target for NSCLC.
- 出版日期2015-10
- 单位中山大学