MicroRNA and mRNA Expression Changes in Steroid Naïve and Steroid Treated DMD Patients

Da Liu, Boryana Stamova, Shengyong Hu, Bradley Ander, Glen C. Jickling, Xinhua Zhan, Frank R Sharp, Brenda Wong

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Background: 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. Objective: This study was designed to identify mRNAs and microRNAs regulated in Duchenne Muscular Dystrophy patients prior to and after steroid therapy. Methods: Genome wide transcriptome profiling of whole blood was performed to identify mRNAs and microRNAs regulated in DMD patients. Results: 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. Conclusions: These identified microRNA-mRNA alterations will help better understand the pathophysiology of DMD and the response to steroid treatment.

Original languageEnglish (US)
Pages (from-to)387-396
Number of pages10
JournalJournal of Neuromuscular Diseases
Volume2
Issue number4
DOIs
StatePublished - Jan 1 2015

Keywords

  • blood
  • Duchenne muscular dystrophy (DMD)
  • microRNA (miRNA)
  • mRNA (gene)

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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