当前位置: X-MOL 学术Mol. Ther. › 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.)
Hypoxic Glioma Cell-Secreted Exosomal miR-301a Activates Wnt/β-catenin Signaling and Promotes Radiation Resistance by Targeting TCEAL7.
Molecular Therapy ( IF 12.4 ) Pub Date : 2019-07-22 , DOI: 10.1016/j.ymthe.2019.07.011
Xiao Yue 1 , Fengming Lan 2 , Tingyi Xia 3
Affiliation  

Recent evidence suggests that microRNAs (miRNAs) can be released to the extracellular microenvironment and mediate cell-cell communication through exosomes. The aim of this study was to identify exosomal miR-301a (exo-miR-301a) involved in glioblastoma (GBM) radioresistance and reveal the possible mechanisms. The exo-miR-301a specifically secreted by hypoxic GBM cells could transfer to corresponding normoxia-cultured cells and promote radiation resistance. Hypoxic exo-miR-301a directly targeted TCEAL7 genes, which were identified as a tumor suppressor in GBM malignancy and actively repressed its' expression in normoxic glioma cells. Our studies indicated that TCEAL7 negatively regulated the Wnt/β-catenin pathway by blocking β-catenin translocation from cytoplasm to nucleus. Interestingly, we clarified that the Wnt/β-catenin signaling was activated by miR-301a and TCEAL7 mediated the important procession. The exo-miR-301a was involved in the resistance to radiotherapy, and the effects would be reversed by miR-301a inhibition or TCEAL7 overexpression to regulate the Wnt/β-catenin axis. Here we show that exo-miR-301a, which is characteristically expressed and secreted by hypoxic glioma cells, is a potent regulator of Wnt/β-catenin and then depresses radiation sensitivity through targeting anti-oncogene TCEAL7. The newly identified exo-miR-301a/TCEAL7-signaling axis could present a novel target for cellular resistance to cancer therapeutic radiation in GBM patients.

中文翻译:

缺氧性胶质瘤细胞分泌的外泌体miR-301a通过靶向TCEAL7激活Wnt /β-catenin信号传导并增强抗辐射性。

最近的证据表明,microRNA(miRNA)可以释放到细胞外微环境,并通过外来体介导细胞间的通讯。这项研究的目的是确定与胶质母细胞瘤(GBM)放射抗性有关的外泌体miR-301a(exo-miR-301a),并揭示可能的机制。低氧GBM细胞特异性分泌的exo-miR-301a可以转移到相应的常氧培养细胞中,并增强抗辐射性。低氧exo-miR-301a直接靶向TCEAL7基因,该基因在GBM恶性肿瘤中被鉴定为肿瘤抑制因子,并积极抑制其在常氧神经胶质瘤细胞中的表达。我们的研究表明,TCEAL7通过阻止β-catenin从细胞质向细胞核的转运来负调控Wnt /β-catenin途径。有趣的是,我们阐明了miR-301a激活了Wnt /β-catenin信号转导,而TCEAL7介导了重要的进程。exo-miR-301a参与了对放射疗法的抵抗,其作用将通过miR-301a抑制或TCEAL7过表达来调节Wnt /β-catenin轴而逆转。在这里,我们显示低氧神经胶质瘤细胞特有表达和分泌的exo-miR-301a是Wnt /β-catenin的有效调节剂,然后通过靶向抗癌基因TCEAL7降低放射敏感性。新近鉴定出的exo-miR-301a / TCEAL7信号转轴可能为GBM患者对癌症治疗性放射线的细胞耐药性提出了新的靶标。并通过miR-301a抑制或TCEAL7过表达来调节Wnt /β-catenin轴来逆转这种作用。在这里,我们显示低氧神经胶质瘤细胞特有表达和分泌的exo-miR-301a是Wnt /β-catenin的有效调节剂,然后通过靶向抗癌基因TCEAL7降低放射敏感性。新近鉴定出的exo-miR-301a / TCEAL7信号转轴可能为GBM患者对癌症治疗性放射线的细胞耐药性提出了新的靶标。并通过miR-301a抑制或TCEAL7过表达来调节Wnt /β-catenin轴来逆转这种作用。在这里,我们显示低氧神经胶质瘤细胞特有表达和分泌的exo-miR-301a是Wnt /β-catenin的有效调节剂,然后通过靶向抗癌基因TCEAL7降低放射敏感性。新近鉴定出的exo-miR-301a / TCEAL7信号转轴可能为GBM患者对癌症治疗性放射线的细胞耐药性提出了新的靶标。
更新日期:2019-07-22
down
wechat
bug