AHIF promotes glioblastoma progression and radioresistance via exosomes

作者：Dai, Xuejun; Liao, Keman; Zhuang, Zhijun; Chen, Binghong; Zhou, Zhiyi; Zhou, Sunhai; Lin, Guoshi; Zhang, Feifei; Lin, Yingying; Miao, Yifeng; Li, Zhiqiang; Huang, Renhua; Qiu, Yongming; Lin, Ruisheng^*

来源：International Journal of Oncology, 2019, 54(1): 261-270.

DOI：10.3892/ijo.2018.4621

• glioblastoma
• antisense transcript of hypoxia-inducible factor 1
• exosome
• progression
• radioresistance

Glioblastoma multiforme (GBM) has the highest mortality rate among patients with brain tumors, and radiotherapy forms an important part of its treatment. Thus, there is an urgent requirement to elucidate the mechanisms conferring GBM progression and radioresistance. In the present study, it was identified that antisense transcript of hypoxia-inducible factor-1 (AHIF) was significantly upregulated in GBM cancerous tissues, as well as in radioresistant GBM cells. The expression of AHIF was also upregulated in response to radiation. Knockdown of AHIF in GBM cells decreased viability and invasive capacities, and increased the proportion of apoptotic cells. By contrast, overexpression of AHIF in GBM cells increased viability and invasive capacities, and decreased the proportion of apoptotic cells. Furthermore, exosomes derived from AHIF-knockdown GBM cells inhibited viability, invasion and radioresistance, whereas exosomes derived from AHIF-overexpressing GBM cells promoted viability, invasion and radioresistance. Further biochemical analysis identified that AHIF regulates factors associated with migration and angiogenesis in exosomes. To the best of our knowledge, the present study is the first to establish that AHIF promotes glioblastoma progression and radioresistance via exosomes, which suggests that AHIF is a potential therapeutic target for GBM.

• 出版日期2019-1
• 单位安徽理工大学; 福建医科大学; 上海交通大学