Liu Da Zhi, Stamova Boryana, Hu Shengyong, Ander Bradley P, Jickling Glen C, Zhan Xinhua, Sharp Frank R, Wong Brenda
Department of Neurology and the M.I.N.D. Institute, University of California at Davis, Sacramento, California, USA.
Division of Pediatric Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
J Neuromuscul Dis. 2015 Sep 22;2(4):387-396. doi: 10.3233/JND-150076.
Duchenne Muscular Dystrophy (DMD) is a recessive X-linked form of muscular dystrophy. Steroid therapy has clinical benefits for DMD patients, but the mechanism remains unclear.
This study was designed to identify mRNAs and microRNAs regulated in Duchenne Muscular Dystrophy patients prior to and after steroid therapy.
Genome wide transcriptome profiling of whole blood was performed to identify mRNAs and microRNAs regulated in DMD patients.
The data show many regulated mRNAs and some microRNAs, including some muscle-specific microRNAs (e.g., miR-206), that were significantly altered in blood of young (age 3-10) DMD patients compared to young controls. A total of 95 microRNAs, but no mRNAs, were differentially expressed in older DMD patients compared to matched controls (age 11-20). Steroid treatment reversed expression patterns of several microRNAs (miR-206, miR-181a, miR-4538, miR-4539, miR-606, and miR-454) that were altered in the young DMD patients. As an example, the over-expression of miR-206 in young DMD patients is predicted to down-regulate a set of target genes (e.g., RHGAP31, KHSRP, CORO1B, PTBP1, C7orf58, DLG4, and KLF4) that would worsen motor function. Since steroids decreased miR-206 expression to control levels, this could provide one mechanism by which steroids improve motor function.
These identified microRNA-mRNA alterations will help better understand the pathophysiology of DMD and the response to steroid treatment.
杜氏肌营养不良症（DMD）是一种隐性X连锁型肌营养不良症。类固醇疗法对DMD患者具有临床益处，但其机制尚不清楚。
本研究旨在鉴定类固醇治疗前后杜氏肌营养不良症患者中受调控的mRNA和微小RNA。
对全血进行全基因组转录组分析，以鉴定DMD患者中受调控的mRNA和微小RNA。
数据显示，许多受调控的mRNA和一些微小RNA，包括一些肌肉特异性微小RNA（如miR-206），在年轻（3至10岁）DMD患者的血液中与年轻对照组相比有显著变化。与匹配的对照组（11至20岁）相比，老年DMD患者共有95种微小RNA差异表达，但没有mRNA差异表达。类固醇治疗逆转了年轻DMD患者中几种微小RNA（miR-206、miR-181a、miR-4538、miR-4539、miR-606和miR-454）的表达模式。例如，预计年轻DMD患者中miR-206的过表达会下调一组靶基因（如RHGAP31、KHSRP、CORO1B、PTBP1、C7orf58、DLG4和KLF4），这些基因会使运动功能恶化。由于类固醇将miR-206的表达降低到对照水平，这可能是类固醇改善运动功能的一种机制。
这些鉴定出的微小RNA-mRNA改变将有助于更好地理解DMD的病理生理学以及对类固醇治疗的反应。
