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

Overview

Journal J Neuromuscul Dis

Publisher Sage Publications

Specialty Neurology

Date 2016 Nov 19

PMID 27858746

Citations 7

Authors

Da Zhi Liu

Boryana Stamova

Shengyong Hu

Bradley P Ander

Glen C Jickling

Xinhua Zhan

Frank R Sharp

Brenda Wong

Affiliations

Soon will be listed here.

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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