MicroRNA‐148a‐3p suppresses epithelial‐to‐mesenchymal transition and stemness properties via Wnt1‐mediated Wnt/β‐catenin pathway in pancreatic cancer

• Published in: Journal of cellular and molecular medicine Vol. 24; no. 22; pp. 13020 - 13035
• Main Authors: Fu, Xiaowei, Hong, Le, Yang, Zhengjiang, Tu, Yi, Xin, Wanpeng, Zha, Ming, Tu, Shuju, Sun, Gen, Li, Yong, Xiao, Weidong
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.11.2020; John Wiley and Sons Inc
• Subjects: Antibodies; Catenin; Cell adhesion & migration; Cell growth; Cell proliferation; Chemotherapy; Cloning; epithelial‐to‐mesenchymal transition; Flow cytometry; Gene expression; Genotype & phenotype; Growth factors; Liver cancer; Mesenchyme; Metastasis; MicroRNAs; miRNA; miR‐148a‐3p; Original; Pancreatic cancer; Pheochromocytoma cells; Proteins; Reagents; stemness properties; Tumorigenesis; Tumors; Wnt protein; Wnt1; Xenografts; miR-148a-3p; pancreatic cancer; stemness properties; Wnt1; epithelial-to-mesenchymal transition
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.15900

Although miR‐148a‐3p has been reported to function as a tumour suppressor in various cancers, the molecular mechanism of miR‐148a‐3p in regulating epithelial‐to‐mesenchymal transition (EMT) and stemness properties of pancreatic cancer (PC) cells remains to be elucidated. In the present study, we demonstrated that miR‐148a‐3p expression was remarkably down‐regulated in PC tissues and cell lines. Moreover, low expression of miR‐148a‐3p was associated with poorer overall survival (OS) in patients with PC. In vitro, gain‐of‐function and loss‐of‐function experiments showed that miR‐148a‐3p suppressed EMT and stemness properties as well as the proliferation, migration and invasion of PC cells. A dual‐luciferase reporter assay demonstrated that Wnt1 was a direct target of miR‐148a‐3p, and its expression was inversely associated with miR‐148a‐3p in PC tissues. Furthermore, miR‐148a‐3p suppressed the Wnt/β‐catenin pathway via down‐regulation of Wnt1. The effects of ectopic miR‐148a‐3p were rescued by Wnt1 overexpression. These biological functions of miR‐148a‐3p in PC were also confirmed in a nude mouse xenograft model. Taken together, these findings suggest that miR‐148a‐3p suppresses PC cell proliferation, invasion, EMT and stemness properties via inhibiting Wnt1‐mediated Wnt/β‐catenin pathway and could be a potential prognostic biomarker as well as a therapeutic target in PC.