Enterovirus 71 (EV71) is an emerging life-threatening pathogen particularly in the Asia-Pacific region. Apoptosis is a major pathogenic feature in EV71 infection. However, which molecular mechanism participating in EV71-induced apoptosis is not completely understood. Long noncoding RNAs (lncRNAs), a newly discovered class of regulatory RNA molecules, govern a wide range of biological functions through multiple regulatory mechanisms. Whether lncRNAs involved in EV71-induced apoptosis was investigated in this study. We conducted an apoptosis-oriented approach by integrating lncRNA and mRNA profilings. lnc-IRAK3-3 is down-regulated in EV71 infection and plays an important role in EV71 infection-induced apoptosis. Compensation of lnc-IRAK3-3 in EV71 infection promoted cell apoptosis wherein GADD45β expression was increased and further triggered caspase3 and PARP cleavage. Using bioinformatics analysis and functional assays, lnc-IRAK3-3 could functionally sequester miR-891b and GADD45β 3'UTR whereas miR-891b showed the inhibitory activity on GADD45β expression. Taken together, lnc-IRAK3-3 has the ability capturing miR-891b to enforce GADD45β expression and eventually promotes apoptosis. On the contrary, host cells suppress lnc-IRAK3-3 to relieve lnc-IRAK3-3-sequestered miR-891b, restrain GADD45β, and attenuate apoptosis in EV71 infection that prevent host cells from severe damages. We discover a new molecular mechanism by which host cells counteract EV71-induced apoptosis through the lnc-IRAK3-3/miR-891b/GADD45β axis partially.

中文翻译：

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宿主缓解了lnc-IRAK3-3杂合的miR-891b，以减弱​​肠病毒71感染中的细胞凋亡。

肠道病毒71（EV71）是一种新兴的威胁生命的病原体，尤其是在亚太地区。凋亡是EV71感染的主要致病特征。但是，尚不完全了解哪种分子机制参与EV71诱导的细胞凋亡。长非编码RNA（lncRNA）是一类新发现的调节RNA分子，它通过多种调节机制控制着广泛的生物学功能。这项研究调查是否lncRNAs参与EV71诱导的细胞凋亡。我们通过整合lncRNA和mRNA分析进行了面向凋亡的方法。lnc-IRAK3-3在EV71感染中下调，并在EV71感染诱导的细胞凋亡中起重要作用。EV71感染中lnc-IRAK3-3的补偿促进了细胞凋亡，其中GADD45β表达增加，并进一步触发caspase3和PARP裂解。使用生物信息学分析和功能分析，lnc-IRAK3-3可以在功能上隔离miR-891b和GADD45β3'UTR，而miR-891b显示出对GADD45β表达的抑制活性。综上所述，lnc-IRAK3-3具有捕获miR-891b来增强GADD45β表达并最终促进细胞凋亡的能力。相反，宿主细胞抑制lnc-IRAK3-3从而减轻lnc-IRAK3-3取代的miR-891b，抑制GADD45β并减弱EV71感染中的凋亡，从而阻止宿主细胞受到严重破坏。我们发现宿主细胞通过lnc-IRAK3-3 / miR-891b /GADD45β轴部分抵消EV71诱导的细胞凋亡的新分子机制。使用生物信息学分析和功能分析，lnc-IRAK3-3可以在功能上隔离miR-891b和GADD45β3'UTR，而miR-891b显示出对GADD45β表达的抑制活性。综上所述，lnc-IRAK3-3具有捕获miR-891b来增强GADD45β表达并最终促进细胞凋亡的能力。相反，宿主细胞抑制lnc-IRAK3-3从而减轻lnc-IRAK3-3取代的miR-891b，抑制GADD45β并减弱EV71感染中的凋亡，从而阻止宿主细胞受到严重破坏。我们发现宿主细胞通过lnc-IRAK3-3 / miR-891b /GADD45β轴部分抵消EV71诱导的细胞凋亡的新分子机制。使用生物信息学分析和功能分析，lnc-IRAK3-3可以在功能上隔离miR-891b和GADD45β3'UTR，而miR-891b显示出对GADD45β表达的抑制活性。综上所述，lnc-IRAK3-3具有捕获miR-891b来增强GADD45β表达并最终促进细胞凋亡的能力。相反，宿主细胞抑制lnc-IRAK3-3从而减轻lnc-IRAK3-3取代的miR-891b，抑制GADD45β并减弱EV71感染中的凋亡，从而阻止宿主细胞受到严重损害。我们发现宿主细胞通过lnc-IRAK3-3 / miR-891b /GADD45β轴部分抵消EV71诱导的细胞凋亡的新分子机制。UTR而miR-891b对GADD45β表达具有抑制活性。综上所述，lnc-IRAK3-3具有捕获miR-891b来增强GADD45β表达并最终促进细胞凋亡的能力。相反，宿主细胞抑制lnc-IRAK3-3从而减轻lnc-IRAK3-3取代的miR-891b，抑制GADD45β并减弱EV71感染中的凋亡，从而阻止宿主细胞受到严重损害。我们发现了一种新的分子机制，宿主细胞通过该分子机制通过lnc-IRAK3-3 / miR-891b /GADD45β轴部分抵消了EV71诱导的细胞凋亡。UTR而miR-891b对GADD45β表达具有抑制活性。综上所述，lnc-IRAK3-3具有捕获miR-891b来增强GADD45β表达并最终促进细胞凋亡的能力。相反，宿主细胞抑制lnc-IRAK3-3从而减轻lnc-IRAK3-3取代的miR-891b，抑制GADD45β并减弱EV71感染中的凋亡，从而阻止宿主细胞受到严重破坏。我们发现宿主细胞通过lnc-IRAK3-3 / miR-891b /GADD45β轴部分抵消EV71诱导的细胞凋亡的新分子机制。并减弱EV71感染中的凋亡，从而阻止宿主细胞受到严重损害。我们发现宿主细胞通过lnc-IRAK3-3 / miR-891b /GADD45β轴部分抵消EV71诱导的细胞凋亡的新分子机制。并减弱EV71感染中的凋亡，从而阻止宿主细胞受到严重损害。我们发现宿主细胞通过lnc-IRAK3-3 / miR-891b /GADD45β轴部分抵消EV71诱导的细胞凋亡的新分子机制。