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

Molecular Medicine

Xinhua Wang¹  Hui Yu¹  Ling Li¹  Feifei Nan¹  Zhenchang Sun¹  Lei Zhang¹  Yu Chang¹  Mingzhi Zhang¹  Jiaqin Yan¹  Xiaoyan Feng¹  Zhaoming Li¹  Jingjing Wu¹  Xiaolong Wu¹  Xiaorui Fu¹  Xudong Zhang¹  Xin Li¹  Junhui Zhang²  Wencai Li³  Renyin Chen³ 

[1]Department of Oncology, The First Affiliated Hospital, Zhengzhou University

[2]Department of Otorhinolaryngology, The Third Affiliated Hospital of Zhengzhou University

[3]Department of pathology, The First Affiliated Hospital, Zhengzhou University

关键词: Astrocyte elevated gene-1 (AEG-1);    T-cell non-Hodgkin’s lymphoma (T-NHL);    Hypoxia;    Autophagy;    Chemosensitivity;   

DOI  :  10.1186/s10020-018-0033-6

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown