J Cancer 2018; 9(12):2147-2159. doi:10.7150/jca.25006

Research Paper

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

Yicheng Xiong1*, Yao Wang2*, Lei Wang2, Yan Huang2,3, Yang Xu2,3, Liancheng Xu2,3, Yibing Guo3, Jingjing Lu3, Xiaohong Li3, Mingyan Zhu2✉, Haixin Qian1✉

1. General Surgery Department, the First Affiliated Hospital of Soochow University, 215006, Suzhou, Jiangsu, P.R. China
2. General Surgery Department, Affiliated Hospital of Nantong University,226001, Nantong, Jiangsu, P.R. China
3. Clinical Medical Research Center, Affiliated Hospital of Nantong University, 226001, Nantong, Jiangsu, P.R. China
*These authors contributed equally to this work.

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Citation:
Xiong Y, Wang Y, Wang L, Huang Y, Xu Y, Xu L, Guo Y, Lu J, Li X, Zhu M, Qian H. MicroRNA-30b targets Snail to impede epithelial-mesenchymal transition in pancreatic cancer stem cells. J Cancer 2018; 9(12):2147-2159. doi:10.7150/jca.25006. Available from http://www.jcancer.org/v09p2147.htm

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Abstract

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 PDAC.

Keywords: miR-30b, pancreatic ductal adenocarcinoma, pancreatic cancer stem cells, epithelial-mesenchymal transition, Snail