Functional Characterization of miR-216a-5p and miR-125a-5p on Pancreatic Cancer Stem Cells

Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related death. Its dismal prognosis is closely related to late diagnosis, which results from both non-specific symptoms and the absence of biomarkers for early diagnosis. MicroRNAs (miRNAs) exert a regulatory role in numerous biological processes and their aberrant expression has been found in a broad spectrum of diseases, including cancer. Cancer stem cells (CSCs) represent a driving force for PDAC initiation, progression and meta-static spread. Our previous research highlighted the interesting behaviour of miR-216a-5p and miR-125a-5p related to PDAC progression and the CSC phenotype. The present study aimed to evaluate the effect of miR-216a-5p and miR-125a-5p on the acquisition or regression of pancreatic CSC traits. BxPC-3, AsPC-1 cell lines, and their CSC-like models were transfected with miR-216a-5p and miR-125a-5p mimic and inhibitor. Following transfection, we evalu-ated the effect of the molecules on the expression of CSC surface markers CD24/CD44/CxCR4, ALDH1 activity, the expression of pluripotency and EMT-related genes and the clonogenic property. Our results showed that miR-216a-5p enhances the expression of CD24/CD44/CxCR4 while negatively affecting the activity of ALDH1 and the expression of EMT genes. MiR-216a-5p positively influenced the clonogenic prop-erty. MiR-125a-5p promoted the expression of CD24/CD44/CxCR4 while inhibiting ALDH1 activity. It enhanced the expression of Snail, Oct-4 and Sox-2 while the clono-genic potential appeared to be affected. Comprehensively, our results provide further knowledge concerning the role of miRNAs in pancreatic CSCs. Furthermore, they corroborate our previous findings about miR-216a-5p potential dual role and miR-125a-5p promotive function in PDAC.