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

摘要

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.