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

研究成果: 雜誌貢獻文章

18 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)802-818
頁數17
期刊Cellular Microbiology
17
發行號6
DOIs
出版狀態已發佈 - 2015 六月 1

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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