Drosophila miR‐5 suppresses Hedgehog signaling by directly targeting Smoothened

Drosophila miR‐5 suppresses Hedgehog signaling by directly targeting Smoothened
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DOI:
10.1016/j.febslet.2012.10.008
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发表时间:
2012-11
期刊:
影响因子:
3.5
通讯作者:
Long Wu;Lei Gao;Xiaomeng Hou;Qinghai Zhang;Shen Li-;Yongfei Yang;Xinhua Lin
Long Wu;Lei Gao;Xiaomeng Hou;Qinghai Zhang;Shen Li-;Yongfei Yang;Xinhua Lin
中科院分区:
生物学3区
文献类型:
--
作者:
Long Wu;Lei Gao;Xiaomeng Hou;Qinghai Zhang;Shen Li-;Yongfei Yang;Xinhua Lin

文献摘要

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Hedgehog(Hh)信号在发育过程和癌症中起着重要作用。Smoothened(Smo)是Hh信号转导通路中的重要信号转导子,其表达受多种转录后机制的调控。然而,microRNAs(miRNAs)是否参与Smo调控仍不清楚。在这里,我们发现miR-5通过靶向Smo作为Hh通路的抑制剂。通过体内传感器实验和体外荧光素酶实验,我们发现miR-5通过直接与Smo的3′UTR结合来下调Smo的表达。此外,我们的数据表明Costal-2(Cos 2)和Fused(Fu)在miR-5介导的Smo减少中不起作用。此外,我们通过检测靶基因的表达,确定miR-5不参与Notch或Dpp信号通路。总之,我们的结果表明,miR-5可以通过直接靶向果蝇中的Smo来特异性抑制Hh信号传导。
Hedgehog (Hh) signaling plays many important roles in developmental processes and cancers. Smoothened (Smo) is an important signal transducer in the Hh pathway, and its expression is tightly regulated by several different post-transcriptional mechanisms. However, whether microRNAs (miRNAs) are involved in Smo regulation is still unclear. Here, we found that miR-5 acts as a suppressor of the Hh pathway by targeting Smo. Through in vivo sensor assay and in vitro luciferase assay, we found that miR-5 downregulates Smo through directly binding to its 3′UTR. Moreover, our data indicated Costal-2 (Cos2) and Fused (Fu) do not play a role in the reduction of Smo mediated by miR-5. Furthermore, we determined that miR-5 not involved in Notch or Dpp signaling pathways by detecting target gene expression. Together, our results indicate that miR-5 can specifically suppress Hh signaling by directly targeting Smo in Drosophila.