Cellular and Molecular Life Sciences

, Volume 70, Issue 2, pp 277–291 | Cite as

MicroRNA-203 enhances Coxsackievirus B3 replication through targeting zinc finger protein-148

  • Maged Gomaa Hemida
  • Xin Ye
  • Huifang M. Zhang
  • Paul J. Hanson
  • Zhen Liu
  • Bruce M. McManus
  • Decheng Yang
Research article

Abstract

Coxsackievirus B3 (CVB3) is the primary causal agent of viral myocarditis. During infection, it hijacks host genes to favour its own replication. However, the underlying mechanism is still unclear. Although the viral receptor is an important factor for viral infectivity, other factors such as microRNAs (miRNA) may also play an essential role in its replication after host cell entry. miRNAs are post-transcriptional gene regulators involved in various fundamental biological processes as well as in diseases. To identify miRNAs involved in CVB3 pathogenesis, we performed microarray analysis of miRNAs using CVB3-infected murine hearts and identified miR-203 as one of the most upregulated candidates. We found that miR-203 upregulation is through the activation of protein kinase C/transcription factor AP-1 pathway. We further identified zinc finger protein-148 (ZFP-148), a transcription factor, as a novel target of miR-203. Ectopic expression of miR-203 downregulated ZFP-148 translation, increased cell viability and subsequently enhanced CVB3 replication. Silencing of ZFP-148 by siRNA showed similar effects on CVB3 replication. Finally, analyses of the signalling cascade downstream of ZFP-148 revealed that miR-203-induced suppression of ZFP-148 differentially regulated the expression of prosurvival and proapoptotic genes of the Bcl-2 family proteins as well as the cell cycle regulators. This altered gene expression promoted cell survival and growth, which provided a favourable environment for CVB3 replication, contributing to the further damage of the infected cells. Taken together, this study identified a novel target of miR-203 and revealed, for the first time, the molecular link between miR-203/ZFP-148 and the pathogenesis of CVB3.

Keywords

MicroRNA-203 ZFP-148 Coxsackievirus B3 Myocarditis 

Abbreviations

CVB3

Coxsackievirus B3

DCM

Dilated cardiomyopathy

DMEM

Dulbecco’s modified Eagle’s medium

miRNA

microRNA

MOI

Multiplicity of infection

PKC

Protein kinase C

pi

Post-infection

pfu

Plaque-forming unit

UTR

Untranslated region

ZFP

Zinc finger protein

Supplementary material

18_2012_1104_MOESM1_ESM.doc (562 kb)
Supplementary material 1 (DOC 561 kb)

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Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Maged Gomaa Hemida
    • 1
  • Xin Ye
    • 1
  • Huifang M. Zhang
    • 1
  • Paul J. Hanson
    • 1
  • Zhen Liu
    • 1
  • Bruce M. McManus
    • 1
  • Decheng Yang
    • 1
  1. 1.Department of Pathology and Laboratory Medicine, The James Hogg Research Center, The Institute for Heart and Lung Health, St. Paul’s HospitalUniversity of British ColumbiaVancouverCanada

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