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AEG-1 is involved in hypoxia-induced autophagy and decreases chemosensitivity in T-cell lymphoma
BACKGROUND: This study was to examine the link between astrocyte elevated gene-1 (AEG-1) and hypoxia induced-chemoresistance in T-cell non-Hodgkin’s lymphoma (T-NHL), as well as the underlying molecular mechanisms. METHODS: Expression of AEG-1, LC3-II, and Beclin-1 were initially examined in human T...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038315/ https://www.ncbi.nlm.nih.gov/pubmed/30134829 http://dx.doi.org/10.1186/s10020-018-0033-6 |
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author | Yan, Jiaqin Zhang, Junhui Zhang, Xudong Li, Xin Li, Ling Li, Zhaoming Chen, Renyin Zhang, Lei Wu, Jingjing Wang, Xinhua Sun, Zhenchang Fu, Xiaorui Chang, Yu Nan, Feifei Yu, Hui Wu, Xiaolong Feng, Xiaoyan Li, Wencai Zhang, Mingzhi |
author_facet | Yan, Jiaqin Zhang, Junhui Zhang, Xudong Li, Xin Li, Ling Li, Zhaoming Chen, Renyin Zhang, Lei Wu, Jingjing Wang, Xinhua Sun, Zhenchang Fu, Xiaorui Chang, Yu Nan, Feifei Yu, Hui Wu, Xiaolong Feng, Xiaoyan Li, Wencai Zhang, Mingzhi |
author_sort | Yan, Jiaqin |
collection | PubMed |
description | BACKGROUND: This study was to examine the link between astrocyte elevated gene-1 (AEG-1) and hypoxia induced-chemoresistance in T-cell non-Hodgkin’s lymphoma (T-NHL), as well as the underlying molecular mechanisms. METHODS: Expression of AEG-1, LC3-II, and Beclin-1 were initially examined in human T-NHL tissues (n = 30) and normal lymph node tissues (n = 16) using western blot, real-time PCR and immunohistochemistry. Western blot was also performed to analyze the expression of AEG-1, LC3-II, and Beclin-1 in T-NHL cells (Hut-78 and Jurkat cells) under normoxia and hypoxia. Additionally, the proliferation and apoptosis of Hut-78 cells exposed to different concentration of Adriamycin (ADM) in normoxia and hypoxia were evaluated by MTT and Annexin-V FITC/PI staining assay. Finally, the effects of AEG-1 on Hut-78 cells exposed to ADM in hypoxia were assessed by MTT and Annexin-V FITC/PI staining assay, and 3-MA (autophagy inhibitor) was further used to determine the underlying mechanism. RESULTS: AEG-1, LC3-II and Beclin-1 expression were significantly increased in T-NHL tissues compared with normal tissues. Incubation of Hut-78 and Jurkat cells in hypoxia obviously increased AEG-1, LC3-II and Beclin-1 expression. Hypoxia induced proliferation and reduced apoptosis of Hut-78 cells exposed to ADM. AEG-1 overexpression further increased proliferation and decreased apoptosis of Hut-78 cells exposed to ADM in hypoxia. Moreover, overexpression of AEG-1 significantly inversed 3-MA induced-changes in cell proliferation and apoptosis of Hut-78 cells exposed to ADM in hypoxia. CONCLUSIONS: This study suggested that AEG-1 is associated with hypoxia-induced T-NHL chemoresistance via regulating autophagy, uncovering a novel target against hypoxia-induced T-NHL chemoresistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s10020-018-0033-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6038315 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60383152018-07-12 AEG-1 is involved in hypoxia-induced autophagy and decreases chemosensitivity in T-cell lymphoma Yan, Jiaqin Zhang, Junhui Zhang, Xudong Li, Xin Li, Ling Li, Zhaoming Chen, Renyin Zhang, Lei Wu, Jingjing Wang, Xinhua Sun, Zhenchang Fu, Xiaorui Chang, Yu Nan, Feifei Yu, Hui Wu, Xiaolong Feng, Xiaoyan Li, Wencai Zhang, Mingzhi Mol Med Research Article BACKGROUND: This study was to examine the link between astrocyte elevated gene-1 (AEG-1) and hypoxia induced-chemoresistance in T-cell non-Hodgkin’s lymphoma (T-NHL), as well as the underlying molecular mechanisms. METHODS: Expression of AEG-1, LC3-II, and Beclin-1 were initially examined in human T-NHL tissues (n = 30) and normal lymph node tissues (n = 16) using western blot, real-time PCR and immunohistochemistry. Western blot was also performed to analyze the expression of AEG-1, LC3-II, and Beclin-1 in T-NHL cells (Hut-78 and Jurkat cells) under normoxia and hypoxia. Additionally, the proliferation and apoptosis of Hut-78 cells exposed to different concentration of Adriamycin (ADM) in normoxia and hypoxia were evaluated by MTT and Annexin-V FITC/PI staining assay. Finally, the effects of AEG-1 on Hut-78 cells exposed to ADM in hypoxia were assessed by MTT and Annexin-V FITC/PI staining assay, and 3-MA (autophagy inhibitor) was further used to determine the underlying mechanism. RESULTS: AEG-1, LC3-II and Beclin-1 expression were significantly increased in T-NHL tissues compared with normal tissues. Incubation of Hut-78 and Jurkat cells in hypoxia obviously increased AEG-1, LC3-II and Beclin-1 expression. Hypoxia induced proliferation and reduced apoptosis of Hut-78 cells exposed to ADM. AEG-1 overexpression further increased proliferation and decreased apoptosis of Hut-78 cells exposed to ADM in hypoxia. Moreover, overexpression of AEG-1 significantly inversed 3-MA induced-changes in cell proliferation and apoptosis of Hut-78 cells exposed to ADM in hypoxia. CONCLUSIONS: This study suggested that AEG-1 is associated with hypoxia-induced T-NHL chemoresistance via regulating autophagy, uncovering a novel target against hypoxia-induced T-NHL chemoresistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s10020-018-0033-6) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-09 /pmc/articles/PMC6038315/ /pubmed/30134829 http://dx.doi.org/10.1186/s10020-018-0033-6 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Yan, Jiaqin Zhang, Junhui Zhang, Xudong Li, Xin Li, Ling Li, Zhaoming Chen, Renyin Zhang, Lei Wu, Jingjing Wang, Xinhua Sun, Zhenchang Fu, Xiaorui Chang, Yu Nan, Feifei Yu, Hui Wu, Xiaolong Feng, Xiaoyan Li, Wencai Zhang, Mingzhi AEG-1 is involved in hypoxia-induced autophagy and decreases chemosensitivity in T-cell lymphoma |
title | AEG-1 is involved in hypoxia-induced autophagy and decreases chemosensitivity in T-cell lymphoma |
title_full | AEG-1 is involved in hypoxia-induced autophagy and decreases chemosensitivity in T-cell lymphoma |
title_fullStr | AEG-1 is involved in hypoxia-induced autophagy and decreases chemosensitivity in T-cell lymphoma |
title_full_unstemmed | AEG-1 is involved in hypoxia-induced autophagy and decreases chemosensitivity in T-cell lymphoma |
title_short | AEG-1 is involved in hypoxia-induced autophagy and decreases chemosensitivity in T-cell lymphoma |
title_sort | aeg-1 is involved in hypoxia-induced autophagy and decreases chemosensitivity in t-cell lymphoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038315/ https://www.ncbi.nlm.nih.gov/pubmed/30134829 http://dx.doi.org/10.1186/s10020-018-0033-6 |
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