DDX3X promotes the biogenesis of a subset of miRNAs and the potential roles they played in cancer development.

DDX3X promotes the biogenesis of a subset of miRNAs and the potential roles they played in cancer development.
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DDX3X 促进 miRNA 子集的生物发生及其在癌症发展中发挥的潜在作用

DOI:
10.1038/srep32739
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发表时间:
2016-09-02
期刊:
影响因子:
4.6
通讯作者:
He Y
He Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhao L;Mao Y;Zhao Y;He Y

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DDX3X位于X染色体上,属于DEAD-box RNA解旋酶家族,作为关键的RNA结合蛋白,在多种生物过程中发挥其调节功能。在本文中,敲低 DDX3X 的表达可以影响一部分 miRNA 的表达水平,尤其是 miR-1、miR-141、miR-145、miR-19b、miR-20a 和 miR-34a。通过采用免疫沉淀(IP)、RNA免疫沉淀(RIP)、双荧光素酶报告基因检测,我们证明DDX3X可以与Drosha/DGCR8复合物相互作用,提高Drosha/DGCR8复合物对pri-miRNA的加工活性,并增加成熟miRNA的表达水平。为了研究DDX3X依赖性miRNA及其下游靶基因在多种癌症中的潜在作用和生物学功能,我们利用癌症基因组图谱(TCGA)、Ingenuity Pathway Analysis(IPA)和多个miRNA靶点预测数据库的原始数据,系统分析了DDX3X依赖性miRNA在近14种癌症与正常组织中的表达水平,并分析了DDX3X依赖性miRNA在多种癌症中的潜在作用和生物学功能。 其假定的下游靶基因的生物学功能。这些发现将为我们深入探讨miRNA生物发生的调控机制提供新的见解和方向,并为有效寻找DDX3X依赖的miRNA及其靶基因在癌症发生中的临床意义和生物学作用提供线索。
DDX3X, located on the X-chromosome, belongs to the DEAD-box RNA helicase family and acts as a key RNA-binding protein to exert its regulatory functions in various biological processes. In this paper, knock-down the expression of DDX3X can affect a subset of miRNA expression levels, especially for miR-1, miR-141, miR-145, miR-19b, miR-20a and miR-34a. Through adopting the immunoprecipitation (IP), RNA immunoprecipitation (RIP), dual luciferase reporter assays, we illustrate that DDX3X could interact with Drosha/DGCR8 complex, elevate the processing activity of Drosha/DGCR8 complex on pri-miRNAs, and increase mature miRNA expression levels. For the studies of potential roles and biological functions of DDX3X-dependent miRNAs and their downstream target genes in multiple cancers, we use the primary data from The Cancer Genome Atlas (TCGA), Ingenuity Pathway Analysis (IPA) and several miRNA target prediction databases, to systematically analyze the expression levels of DDX3X-dependent miRNAs in almost 14 kinds of cancers versus normal tissues, and the essential biological functions for their putative downstream target genes. All these findings will provide us novel insights and directions for thoroughly exploring the regulatory mechanisms of miRNA biogenesis, and shed light on effectively searching the clinical significances and biological roles of DDX3X-dependent miRNAs and their target genes in cancer development.
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影响因子: --
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