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DDX3X 促进了一组 miRNA 的生物发生,以及它们在癌症发展中可能发挥的作用。

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

机构信息

Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Department of Pathology, School of Basic Medical Science, Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China.

出版信息

Sci Rep. 2016 Sep 2;6:32739. doi: 10.1038/srep32739.

Abstract

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.

摘要

DDX3X 位于 X 染色体上,属于 DEAD -box RNA 解旋酶家族,作为一种关键的 RNA 结合蛋白,在各种生物过程中发挥其调节功能。在本文中,敲低 DDX3X 的表达可以影响一小部分 miRNA 的表达水平,特别是 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等方法,我们阐明了 DDX3X 可以与 Drosha/DGCR8 复合物相互作用,提高 Drosha/DGCR8 复合物对 pri-miRNAs 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,我们使用了来自癌症基因组图谱(TCGA)、Ingenuity 通路分析(IPA)和几个 miRNA 靶基因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,以及它们潜在下游靶基因的重要生物学功能。所有这些发现将为我们深入探索 miRNA 生物发生的调节机制提供新的见解和方向,并为有效寻找 DDX3X 依赖性 miRNA 和其靶基因在癌症发展中的临床意义和生物学作用提供线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e45b/5009351/9e7795daab7f/srep32739-f1.jpg

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