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

机译:miR-375通过靶向YAP1抑制小鼠胰腺祖细胞的增殖

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biBackground/Aims /i/bThe 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. biMethods /i/bThe spatio-temporal expression pattern of YAP1 in mouse developing pancreata was detected by iin situ/i 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. biResults /i/bWe 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. biConclusion /i/bOur 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.
机译:背景/目标 Hippo信号通路在器官发育和组织再生过程中调节干细胞和组织祖细胞的扩增和分化。先前的研究表明,HAP信号通路的有效效应子YAP1在胰腺发育中起着至关重要的作用,但在胰腺祖细胞中YAP1的功能却鲜为人知。 方法 通过原位杂交检测YAP1在小鼠胰腺发育中的时空表达模式。通过CCK-8分析和Ki67免疫染色分析了沉默YAP1对胰腺祖细胞增殖的影响。通过双重荧光素酶报告基因测定,QRT-PCR和western blot测定miR-375对YAP1表达的调节。最后,通过CCK-8分析和Ki67免疫染色分析了miR-375对胰腺祖细胞增殖的影响。 结果 我们发现YAP1在胚胎和成年胰腺祖细胞中高表达。 siRNA抑制YAP1抑制了胰腺祖细胞的增殖。小鼠YAP1是miR-375的靶基因,而miR-375可以靶向YAP1 mRNA的3'UTR以降低其蛋白质和mRNA水平。与通过siRNA沉默YAP1相似,miR-375显着抑制了胰腺祖细胞的增殖。 结论 我们的结果表明,YAP1是胰腺祖细胞增殖所必需的,而miR-375参与调节胰腺祖细胞分化过程中YAP1的表达。

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