当前位置: X-MOL 学术Oncogenesis › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
miR-18a promotes glioblastoma development by down-regulating ALOXE3-mediated ferroptotic and anti-migration activities
Oncogenesis ( IF 6.2 ) Pub Date : 2021-02-12 , DOI: 10.1038/s41389-021-00304-3
Xinzhi Yang , Jiangang Liu , Chenci Wang , Kenneth King-yip Cheng , Hongchao Xu , Qingzhong Li , Tian Hua , Xue Jiang , Lili Sheng , Jie Mao , Zhuohao Liu

The development of glioblastoma (GBM) is typically accompanied by marked changes in lipid metabolism. Oxylipins and their catalyzed enzymes lipoxygenases (LOXs) have been shown to participate in the development of cancers via multiple pathways, while the understanding of LOXs in GBM remains enigmatic. Thus, we aimed to explore the expression and functional roles of LOXs in the development of GBM. Here we showed that ALOXE3 was markedly down-regulated in human GBM. Knockdown of ALOXE3 in GBM cells fostered the orthotopic tumor growth and shortened lifespan in mice. ALOXE3 deficiency rendered GBM cells resistant to p53-SLC7A11 dependent ferroptosis, promoting GBM cell survival. Mechanistically, miR-18a directly targeted ALOXE3 and suppressed its expression and functions in GBM cells. Furthermore, ALOXE3 silencing promoted 12-hydroxyeicosatetraenoic acids (12-HETE) secretion from GBM cells, in turn, 12-HETE enhanced migration of GBM cells by activating Gs-protein-coupled receptor (GsPCR)-PI3K-Akt pathway in an autocrine manner. Altogether, miR-18a/ALOXE3 axis exerts tumor promoting functions by regulating ferroptosis and migration of GBM cells. Targeting miR-18a/ALOXE3 axis may provide novel therapeutic approaches for GBM treatment.



中文翻译:

miR-18a通过下调ALOXE3介导的促肥大和抗迁移活性来促进胶质母细胞瘤的发展

胶质母细胞瘤(GBM)的发展通常伴随着脂质代谢的明显变化。脂氧合蛋白及其催化的酶脂氧合酶(LOXs)已显示出通过多种途径参与癌症的发展,而对GBM中LOXs的理解仍然是个谜。因此,我们旨在探讨LOX在GBM开发中的表达及其功能。在这里,我们显示了ALOXE3在人GBM中明显下调。敲除GBM细胞中的ALOXE3可促进原位肿瘤生长,并缩短小鼠的寿命。ALOXE3缺乏使GBM细胞对p53-SLC7A11依赖的肥大病具有抗性,从而促进GBM细胞存活。机械上,miR-18a直接靶向ALOXE3并抑制其在GBM细胞中的表达和功能。此外,s-蛋白偶联受体(G s PCR)-PI3K-Akt途径以自分泌方式进行。总而言之,miR-18a / ALOXE3轴通过调节肥大病和GBM细胞的迁移发挥肿瘤促进功能。靶向miR-18a / ALOXE3轴可能为GBM治疗提供新的治疗方法。

更新日期:2021-02-15
down
wechat
bug