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

  • Author(s): Liu, Da Zhi
  • Stamova, Boryana
  • Hu, Shengyong
  • Ander, Bradley P
  • Jickling, Glen C
  • Zhan, Xinhua
  • Sharp, Frank R
  • Wong, Brenda
  • et al.
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.

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