miR-375 Inhibits Proliferation of Mouse Pancreatic Progenitor Cells by Targeting YAP1

Background/Aims: The Hippo signaling pathway regulates expansion and differentiation of stem cells and tissue progenitor cells during organ development and tissue regeneration. Previous studies have shown that YAP1, a potent effector of the Hippo signaling pathway, plays a crucial role in pancreas development, but the function of YAP1 in pancreatic progenitor cells is less known. Methods: The spatio-temporal expression pattern of YAP1 in mouse developing pancreata was detected by in situ hybridization. The effect of silencing YAP1 on the proliferation of pancreatic progenitor cells was analyzed by CCK-8 assay and Ki67 immunostaining. The regulation of miR-375 on YAP1 expression was determined by dual luciferase reporter assay, QRT-PCR and western blot. Finally, the influence of miR-375 on proliferation of pancreatic progenitor cells was analyzed by CCK-8 assay and Ki67 immunostaining. Results: We found that YAP1 was highly expressed in embryonic and adult pancreatic progenitor cells. Knocking down YAP1 by siRNA inhibited the proliferation of pancreatic progenitor cells. The mouse YAP1 was a target gene of miR-375, and miR-375 could target the 3' UTR of YAP1 mRNA to decrease its protein and mRNA levels. Similar to silencing YAP1 by siRNA, the proliferation of pancreatic progenitor cells was inhibited significantly by miR-375. Conclusion: Our results indicate that YAP1 is necessary for the proliferation of pancreatic progenitor cells and miR-375 participates in regulating YAP1 expression during pancreatic progenitor cells differentiation. Copyright (C) 2013 S. Karger AG, Basel