...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Cellular Physiology >Differential Expression of miR-4520a Associated With Pyrin Mutations in Familial Mediterranean Fever (FMF)
【24h】

Differential Expression of miR-4520a Associated With Pyrin Mutations in Familial Mediterranean Fever (FMF)

机译：微分mir - 4520 a的表达相关在地中海Pyrin突变发烧(FMF)

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent, acute, and self-limiting attacks of fever. Mutations in MEFV gene encoding pyrin account for FMF, but the high number of heterozygote patients with typical symptoms of the disease has driven a number of alternative aetiopathogenic hypotheses. The MEFV gene was knocked down in human myelomonocytic cells that express endogenous pyrin to identify deregulated microRNAs (miRNAs). Microarray analyses revealed 29 significantly differentially expressed miRNAs implicated in pathways associated with cellular integrity and survival. Implementation of in silico gene network prediction algorithms and bioinformatics analyses showed that miR-4520a is predicted to target genes implicated in autophagy through regulation of RHEB/mTOR signaling. Differential expression levels of RHEB were confirmed by luciferase reporter gene assays providing further evidence that is directly targeted by miR-4520a. Although the relative expression levels of miR-4520a were variable among FMF patients, the statistical expression of miR-4520a was different between FMF mutation carriers and controls (P = 0.0061), indicating an association between miR-4520a expression and MEFV mutations. Comparison between FMF patients bearing the M694V mutation, associated with severe disease, and healthy controls showed a significant increase in miR-4520a expression levels ( P = 0.00545). These data suggest that RHEB, the main activator of mTOR signaling, is a valid target of miR-4520a with the relative expression levels of the latter being significantly deregulated in FMF patients and highly dependent on the presence of pyrin mutations, especially of the M694V type. These results suggest a role of deregulated autophagy in the pathogenesis of FMF.(C) 2016 Wiley Periodicals, Inc.
机译：家族性地中海热(FMF)是一种常染色体隐性疾病复发,发烧急性、自限性的攻击。MEFV突变基因编码pyrin占FMF,但大量的杂合子患者疾病导致的典型症状数量的替代aetiopathogenic假设。MEFV基因在人类撞倒了myelomonocytic表达内源性的细胞pyrin识别管制小分子核糖核酸(microrna)。微阵列分析显示29显著差异表达microrna卷入通路与细胞完整性和有关生存。网络预测算法和生物信息学分析表明,mir - 4520——预计目标基因与自噬通过监管RHEB / mTOR的信号。表达水平RHEB被证实了荧光素酶报告基因分析进一步提供证据表明,直接mir - 4520 a的目标。尽管的相对表达水平mir - 4520 a是变量FMF患者统计mir - 4520 a的表达是不同的FMF之间突变携带者和控制(P =0.0061),表明之间的关联mir - 4520 a表达和MEFV突变。对比FMF病人M694V轴承突变,与严重疾病有关,健康对照组有显著提高mir - 4520 a表达水平(P = 0.00545)。数据表明,RHEB的主要催化剂mTOR信号,是一个有效的目标mir - 4520 a后者的相对表达水平被显著管制FMF的病人和高度依赖pyrin的存在突变,尤其是M694V类型的。结果表明对自噬的作用FMF的发病机制。(C) 2016威利期刊、公司。

著录项

相似文献

  • 外文文献
  • 中文文献
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号