miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes.
miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes.
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miR-16 家族通过调节多个细胞周期基因诱导细胞周期停滞。
DOI：
10.1093/nar/gkn522
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发表时间：
2008-09
影响因子：
14.9
通讯作者：
Zheng X
中科院分区：
文献类型：
--
作者：
Liu Q;Fu H;Sun F;Zhang H;Tie Y;Zhu J;Xing R;Sun Z;Zheng X
MicroRNAs(MiRNAs)是一类被认为通过调节基因表达而参与多种生物学过程的小调节RNA。在各种物种中已经发现了大量的miRNAs，还有更多的miRNAs有待检测。一般来说，数百个mRNAs被预测为一个miRNA的潜在靶标，因此识别真正的miRNA靶标是一个巨大的挑战。在这里，我们建立了DROSHA蛋白缺失的细胞系，并筛选了数十个受miRNA介导的RNA沉默途径潜在调控的转录本(包括Cyclin D1)。在构建miRNA表达文库的基础上，建立了利用荧光素酶报告基因反向筛选miRNA靶标的方法。通过这种方法，我们发现Cyclin D1(CCND1)的表达直接受miR-16家族的调控，并且miR-16部分地通过CCND1诱导A549细胞的G1期停滞。此外，还发现了几个受miR-16家族调控的细胞周期基因，包括Cyclin D3(CCND3)、Cyclin E1(CCNE1)和CDK6。综上所述，我们的数据表明miR-16家族通过同时沉默多个细胞周期基因而不是单个靶点来触发G0/G1期细胞的积累。
MicroRNAs (miRNAs) are a class of small regulatory RNAs that are thought to be involved in diverse biological processes by regulating gene expression. Numerous miRNAs have been identified in various species, and many more miRNAs remain to be detected. Generally, hundreds of mRNAs have been predicted to be potential targets of one miRNA, so it is a great challenge to identify the genuine miRNA targets. Here, we generated the cell lines depleted of Drosha protein and screened dozens of transcripts (including Cyclin D1) regulated potentially by miRNA-mediated RNA silencing pathway. On the basis of miRNA expressing library, we established a miRNA targets reverse screening method by using luciferase reporter assay. By this method, we found that the expression of Cyclin D1 (CCND1) was regulated by miR-16 family directly, and miR-16 induced G1 arrest in A549 cells partially by CCND1. Furthermore, several other cell cycle genes were revealed to be regulated by miR-16 family, including Cyclin D3 (CCND3), Cyclin E1 (CCNE1) and CDK6. Taken together, our data suggests that miR-16 family triggers an accumulation of cells in G0/G1 by silencing multiple cell cycle genes simultaneously, rather than the individual target.
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影响因子：
30.8
作者：
Bentwich, I;Avniel, A;Bentwich, Z
通讯作者：
Bentwich, Z
影响因子：
64.8
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.
影响因子：
5.6
作者：
Bottoni, A;Piccin, D;Uberti, ECD
通讯作者：
Uberti, ECD
Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ