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

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

Research output: Contribution to journalArticlepeer-review

7 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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