GATA1/SP1 and miR-874 mediate enterovirus-71-induced apoptosis in a granzyme-B-dependent manner in Jurkat cells
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ORIGINAL ARTICLE
GATA1/SP1 and miR‑874 mediate enterovirus‑71‑induced apoptosis in a granzyme‑B‑dependent manner in Jurkat cells Meijuan Zhang1 · Ying Chen1 · Xiangjun Cheng1 · Zhenzhen Cai1 · Shengfeng Qiu1 Received: 20 April 2020 / Accepted: 21 July 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract Enterovirus 71 (EV71)-induced T lymphocyte apoptosis plays an important role in hand, foot, and mouth disease (HFMD), and granzyme B (GZMB) has been shown to be critical for this process. However, the mechanisms underlying GZMBmediated apoptosis of T lymphocytes remain unknown. In this study, we investigated whether transcription factors and microRNAs (miRNAs) are involved in GZMB-mediated apoptosis of T lymphocytes in response to EV71 infection. Our findings indicated that EV71 infection significantly induced apoptosis in Jurkat cells, a human T lymphocytes cell line, as revealed in flow cytometric analysis. Furthermore, EV71 increased the expression of pro-apoptosis Bcl-2-associated X (Bax) and cleaved caspase 3 but decreased the expression of anti-apoptosis B-cell lymphoma protein 2 (Bcl2). GZMB knockdown decreased cell apoptosis and prevented EV71-induced changes in the expression of Bax, cleaved caspase 3, and Bcl2 in Jurkat cells, highlighting the role of GZMB as a key factor in EV71-induced apoptosis. Our study also indicated that overexpression of the transcription factors GATA binding factor 1 (GATA1) and specificity protein 1 (SP1) significantly increased luciferase activity when this gene was inserted in the GZMB 3’ untranslated region (3’UTR). GATA1/SP1 overexpression induced cell apoptosis, increased the expression of Bax and cleaved caspase 3, and decreased the expression of Bcl2. Finally, our results suggested that miR-874 plays an essential role in GZMB-mediated cell apoptosis, since an miR-874 mimic decreases the expression of GZMB by targeting its 3’UTR. Collectively, these data indicated that GATA1/SP1 and miR-874 mediate EV71-induced apoptosis in a granzyme B-dependent manner. This signaling pathway may provide a new pharmacological target for the prevention and treatment of HFMD.
Introduction Although hand, foot, and mouth disease (HFMD) is commonly asymptomatic or manifests benign symptoms, this disease can result in severe neurological disorders. Enterovirus 71 (EV71) is a single-positive-stranded RNA virus belonging to the genus Enterovirus of the family Handling Editor: Akbar Dastjerdi. Meijuan Zhang and Ying Chen are co-first authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00705-020-04783-4) contains supplementary material, which is available to authorized users. * Shengfeng Qiu [email protected] 1
Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, Jiangsu, China
Picornaviridae [3, 38]. Accumulating data have demonstrated that EV71 is one of the predominant causative pathogens of HFMD. Similar to poliovirus,
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