WEE1 is a validated target of the microRNA miR-17-92 cluster in leukemia.

WEE1 is a validated target of the microRNA miR-17-92 cluster in leukemia.
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DOI:
10.1016/j.cancergen.2015.01.001
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发表时间:
2015-05
期刊:
影响因子:
1.9
通讯作者:
Zeleznik-Le NJ
Zeleznik-Le NJ
中科院分区:
医学4区
文献类型:
--
作者:
Brockway S;Zeleznik-Le NJ

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MicroRNA是短的单链RNA,其通过与其mRNA靶的3'非翻译区中的互补位点结合来调节靶基因表达。编码miR-17、miR-18 a、miR-19 a、miR-20 a、miR-19 b和miR-92 a的多顺反子miR-17-92簇先前显示在多种类型的癌症中过表达。在本研究中,使用靶基因预测算法来预测miR-17-92簇的潜在靶点。WEE 1是一种抑制细胞周期进程的激酶,被鉴定为该簇六种miRNA中五种的可能靶点。使用荧光素酶报告基因测定来确定miR-17、miR-20 a和miR-18 a特异性靶向WEE 1的3' UTR的核苷酸465至487,而miR-19 a和miR-19 b通过靶向核苷酸1069至1091对WEE 1发挥控制作用。在同一组细胞系中,内源性miR-17或miR-19 a表达与内源性WEE 1蛋白表达之间确定负相关。我们得出结论,WEE 1是白血病中miR-17-92簇的有效靶点。
MicroRNAs are short single-stranded RNAs that regulate target gene expression by binding to complementary sites in the 3’ untranslated region of their mRNA targets. The polycistronic miR-17-92 cluster, which encodes miR-17, miR-18a, miR-19a, miR-20a, miR-19b, and miR-92a, was previously shown to be overexpressed in multiple types of cancer. In the present study, target gene prediction algorithms were used to predict potential targets of the miR-17-92 cluster. WEE1, a kinase that inhibits cell cycle progression, was identified as a possible target of five of the six miRNAs of the cluster. Luciferase reporter assays were used to determine that miR-17, miR-20a, and miR-18a specifically target nucleotides 465 to 487 of the 3’ UTR of WEE1, while miR-19a and miR-19b exert control on WEE1 by targeting nucleotides 1069 to 1091. A negative correlation was determined between endogenous miR-17 or miR-19a expression and endogenous WEE1 protein expression in the same panel of cell lines. We conclude that WEE1 is a valid target of the miR-17-92 cluster in leukemia.
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