miR-375 Inhibits Proliferation of Mouse Pancreatic Progenitor Cells by Targeting YAP1
miR-375 Inhibits Proliferation of Mouse Pancreatic Progenitor Cells by Targeting YAP1
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miR-375 通过靶向 YAP1 抑制小鼠胰腺祖细胞的增殖
DOI：
10.1159/000356614
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发表时间：
2013-12
影响因子：
--
通讯作者：
Teng, Chun-Bo
中科院分区：
文献类型：
--
作者：
Feng, Rui-Cheng;Li, Yun-Chao;Zhou, Di;Teng, Chun-Bo
背景/目标：Hippo信号通路调节器官发育和组织再生过程中干细胞和组织祖细胞的扩增和分化。以前的研究表明，YAP 1是Hippo信号通路的有效效应子，在胰腺发育中起着至关重要的作用，但YAP 1在胰腺祖细胞中的功能鲜为人知。方法：采用原位杂交技术检测YAP 1在小鼠胰腺发育过程中的时空表达。采用CCK-8法和Ki 67免疫组化法分析沉默YAP 1对胰腺祖细胞增殖的影响。采用双荧光素酶报告基因分析、定量RT-PCR和western blot检测miR-375对YAP 1表达的调控作用。最后，采用CCK-8法和Ki 67免疫组化法分析miR-375对胰腺前体细胞增殖的影响。结果：发现YAP 1在胚胎和成人胰腺祖细胞中高表达。通过siRNA敲除YAP 1抑制胰腺祖细胞的增殖。小鼠YAP 1是miR-375的靶基因，miR-375可以靶向YAP 1 mRNA的3' UTR，降低其蛋白和mRNA水平。与通过siRNA沉默YAP 1类似，miR-375显著抑制胰腺祖细胞的增殖。结论：我们的研究结果表明，YAP 1是胰腺祖细胞增殖所必需的，miR-375参与调节胰腺祖细胞分化过程中YAP 1的表达。
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.
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影响因子：
8
作者：
Ehsanian, R.;Brown, M.;Lu, H.;Yang, X. P.;Pattatheyil, A.;Yan, B.;Duggal, P.;Chuang, R.;Doondeea, J.;Feller, S.;Sudol, M.;Chen, Z.;Van Waes, C.
通讯作者：
Van Waes, C.
DOI：
10.1073/pnas.0912589107
发表时间：
2010-01-05
影响因子：
11.1
作者：
Rovira, Meritxell;Scott, Sherri-Gae;Leach, Steven D.
通讯作者：
Leach, Steven D.
影响因子：
10.5
作者：
Zhao, Bin;Li, Li;Guan, Kun-Liang
通讯作者：
Guan, Kun-Liang
影响因子：
10.5
作者：
Vassilev, A;Kaneko, KJ;DePamphilis, ML
通讯作者：
DePamphilis, ML
yes相关蛋白的过度表达导致非小细胞肺癌的进展和不良预后
影响因子：
5.7
作者：
Wang, Yang;Dong, Qianze;Qiu, Xueshan
通讯作者：
Qiu, Xueshan