■强直性肌营养不良1型(DM1)是成人中最常见的肌营养不良,然而,目前还没有改善疾病的治疗方法。miRNA表达中断可能导致靶mRNA的失调和参与DM1致病机制的功能障碍。
我们使用微阵列平台来检查源自DM1患者和匹配对照的骨骼肌活检中的miRNA/mRNA表达谱。进行生物信息学分析和双荧光素酶报告基因测定以提供对DM1中改变的miRNA-mRNA调控网络的洞察。
■鉴定了23个差异表达的miRNA和135个差异表达的基因。qPCR证实miR-3201、生肌因子5(MYF5)、肌源性分化1(MYOD1),CUGBP,Elav-like家族成员1(CELF1),CELF2显著上调,而miR-196a,miR-200c,和miR-146a显著下调。丰富的功能和途径,如多细胞生物发育,RNA剪接,细胞分化,和剪接体与DM1有关。miRNA-mRNA相互作用网络显示miR-182、miR-30c-2和miR-200c是可能与hub基因相互作用的关键节点。荧光素酶报告基因测定证实了miR-196a和CELF2之间的直接相互作用。
■这些结果表明,观察到的miRNA/mRNA失调可能有助于与DM1发病机制相关的特定功能和途径,强调miR-196a和CELF2的功能障碍。
UNASSIGNED: Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults, yet there are currently no disease-modifying treatments. Disrupted miRNA expressions may lead to dysregulation of target mRNAs and dysfunction involved in DM1 pathogenic mechanism.
UNASSIGNED: We used microarray platforms to examine the miRNA/mRNA expression profiles in skeletal muscle biopsies derived from DM1 patients and matched controls. Bioinformatics analysis and dual-luciferase reporter assay were conducted to provide insight into miRNA-mRNA regulatory networks altered in DM1.
UNASSIGNED: Twenty-three differentially expressed miRNAs and 135 differentially expressed genes were identified. qPCR confirmed that miR-3201, myogenic factor 5 (MYF5), myogenic differentiation 1 (MYOD1), CUGBP, Elav-like family member 1 (CELF1), and CELF2 were significantly up-regulated, while miR-196a, miR-200c, and miR-146a were significantly down-regulated. Enriched functions and pathways such as multicellular organismal development, RNA splicing, cell differentiation, and spliceosome are relevant to DM1. The miRNA-mRNA interaction network revealed that miR-182, miR-30c-2, and miR-200c were the critical nodes that potentially interacted with hub genes. Luciferase reporter assay confirmed the direct interaction between miR-196a and CELF2.
UNASSIGNED: Those results implied that the observed miRNA/mRNA dysregulation could contribute to specific functions and pathways related to DM1 pathogenesis, highlighting the dysfunction of miR-196a and CELF2.