AEG-1 is involved in hypoxia-induced autophagy and decreases chemosensitivity in T-cell lymphoma

作者：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^*

来源：Molecular Medicine, 2018, 24(1): 35.

DOI：10.1186/s10020-018-0033-6

• Astrocyte elevated gene-1 (AEG-1)
• T-cell Hodgkin's lymphoma (T-NHL)
• Hypoxia
• Autophagy
• Chemosensitivity

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 prolifesation 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.

• 出版日期2018-7-9
• 单位郑州大学