miR-146a and miR-370 coordinate enterovirus 71-induced cell apoptosis through targeting SOS1 and GADD45β

Ya Ling Chang, Bing Ching Ho, Singh Sher, Sung Liang Yu, Pan Chyr Yang

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Enterovirus 71 (EV71) is an emerging life-threatening pathogen particularly in the Asia-Pacific region. The major pathogenic feature in EV71-infected cells is apoptosis. However, which molecular mechanism mainly contributes to EV71-induced apoptosis is not investigated thoroughly. MicroRNAs (MiRNAs), the newly discovered molecules, govern a wide range of biological functions through post-transcriptional regulation including viral pathogenesis. Whether miRNAs and messenger RNAs (mRNAs) coordinate to trigger host cell apoptosis in EV71 infection was investigated in this study. We conducted an apoptosis-oriented approach using both mRNA and miRNA profiling and bioinformatic analysis. We identified two major apoptosis-associated signalling pathways, Bcl2 antagonist of cell death (BAD) phosphorylation and p53-dependent apoptosis pathways, in which Son of sevenless homolog 1 (SOS1) and Growth arrest and DNA damage-inducible protein 45β (GADD45β) were predicted as targets of miR-146a and miR-370 respectively. Luciferase reporter assays and Western blots demonstrated the negative regulation between miR-146a and SOS1 and between miR-370 and GADD45β. Silencing of miR-146a restored SOS1 expression and partially attenuated EV71 infection-induced apoptosis. Conversely, ectopic expression of miR-370 decreased virus infection-induced GADD45β expression and also diminished apoptosis. Finally, the transfection of antagomiR-146a and miR-370 contributed to attenuating EV71 infection-induced apoptosis. Herein we clearly demonstrate that EV71-induced cell apoptosis is partly governed by altered miRNAs.

Original languageEnglish
Pages (from-to)802-818
Number of pages17
JournalCellular Microbiology
Volume17
Issue number6
DOIs
Publication statusPublished - 2015 Jun 1

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SOS1 Protein
Enterovirus
DNA Damage
Apoptosis
Growth
Enterovirus Infections
Proteins
MicroRNAs
Messenger RNA
Virus Diseases

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

Cite this

miR-146a and miR-370 coordinate enterovirus 71-induced cell apoptosis through targeting SOS1 and GADD45β. / Chang, Ya Ling; Ho, Bing Ching; Sher, Singh; Yu, Sung Liang; Yang, Pan Chyr.

In: Cellular Microbiology, Vol. 17, No. 6, 01.06.2015, p. 802-818.

Research output: Contribution to journalArticle

Chang, Ya Ling ; Ho, Bing Ching ; Sher, Singh ; Yu, Sung Liang ; Yang, Pan Chyr. / miR-146a and miR-370 coordinate enterovirus 71-induced cell apoptosis through targeting SOS1 and GADD45β. In: Cellular Microbiology. 2015 ; Vol. 17, No. 6. pp. 802-818.
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