MicroRNA-30b targets Snail to impede epithelial-mesenchymal transition in pancreatic cancer stem cells

作者：Yicheng Xiong, Yao Wang, Lei Wang, Yan Huang, Yang Xu, Liancheng Xu, Yibing Guo, Jingjing Lu, Xiaohong Li, Mingyan Zhu, Haixin Qian · 发表于：Journal of Cancer · 年份：2018 · DOI：10.7150/jca.25006 · 被引用次数：39 · 研究领域：Cancer Cells and Metastasis、MicroRNA in disease regulation、Hydrogen's biological and therapeutic effects

Snail-mediated epithelial-mesenchymal transition (EMT) process plays a fundamental role in facilitating pancreatic ductal adenocarcinoma (PDAC) stemness and metastasis. In the present study, we revealed that microRNA-30 (miR-30) members, especially miR-30b, were remarkably downregulated in triple-positive (CD24 + , CD44 + , EpCAM + ) pancreatic cancer stem cells (PCSCs). In addition, we revealed that miR-30b suppressed EMT process in PCSCs. Overexpression of miR-30b led to reduced expression of mesenchymal marker N-cadherin and the upregulation of epithelial marker E-cadherin. Moreover, both of TargetScan and PicTar algorithms predicted that miR-30b directly targeted Snail 3'UTR. Luciferase reporter assay showed that miR-30b could specifically reduce the translational activity of Snail wild-type 3'UTR, but not its mutant form. In line with these results, transwell assay demonstrated that overexpression of miR-30b mimic impaired migratory and invasive capacities of PCSCs. Furthermore, miR-30b overexpression suppresses in vivo tumorigenic potential of PDACs. Finally, a negative correlation between the expression of miR-30b and Snail was uncovered. Low level of miR-30b and high Snail expression both predict dismal prognosis in PDAC patients. Taken together, these findings implicate that miR-30b may suppress PCSC phenotype and PDAC metastasis through posttranscriptionally suppressing Snail expression, highlighting that miR-30b may serve as a therapeutic agent in the treatment of ...