靶向波形蛋白的致癌ZEB2/miR-637/HMGA1信号轴促进神经胶质瘤的恶性表型,Molecular Therapy - Nucleic Acids

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靶向波形蛋白的致癌ZEB2/miR-637/HMGA1信号轴促进神经胶质瘤的恶性表型
Molecular Therapy - Nucleic Acids ( IF 6.5 ) Pub Date : 2021-01-05 , DOI: 10.1016/j.omtn.2020.12.029
Yu Zeng , Tianshi Que , Jie Lin , Zhengming Zhan , Anqi Xu , Zhiyong Wu , Cheng Xie , Jie Luo , Shengfeng Ding , Hao Long , Xian Zhang , Ye Song

神经胶质瘤是中枢神经系统最常见的原发性肿瘤。我们之前证实锌指E盒结合同源盒（ZEB）2促进神经胶质瘤的恶性进展，而microRNA-637（miR-637）与神经胶质瘤的良好预后相关。本研究旨在探讨胶质瘤中ZEB2与miR-637及其下游信号通路之间的潜在相互作用。结果表明ZEB2可以直接结合miR-637启动子中的E-box元件，并通过下调miR-637促进细胞增殖、迁移和侵袭。随后的筛选证实HMGA1是miR-637的直接靶标，而miR-637可以通过抑制HMGA1和来驱动胶质瘤的恶性表型。此外，观察到细胞质 HMGA1 和波形蛋白之间的相互作用，抑制波形蛋白可以消除 HMGA1 过表达诱导的迁移和侵袭增加。 HMGA1 和波形蛋白均与神经胶质瘤的不良预后相关。此外，在异柠檬酸脱氢酶 (IDH) 野生型和 1p/19q 非共缺失弥漫性浸润性神经胶质瘤中发现 HMGA1 和波形蛋白上调。总之，我们确定了一个靶向波形蛋白的致癌 ZEB2/miR-637/HMGA1 信号轴，可促进神经胶质瘤的迁移和侵袭。

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Oncogenic ZEB2/miR-637/HMGA1 signaling axis targeting vimentin promotes the malignant phenotype of glioma

Glioma is the most common primary tumor of the central nervous system. We previously confirmed that zinc finger E-box binding homeobox (ZEB) 2 promotes the malignant progression of glioma, while microRNA-637 (miR-637) is associated with favorable prognosis in glioma. This study aimed to investigate the potential interaction between ZEB2 and miR-637 and its downstream signaling pathway in glioma. The results revealed that ZEB2 could directly bind to the E-box elements in the miR-637 promoter and promote cell proliferation, migration, and invasion via miR-637 downregulation. Subsequent screening confirmed that HMGA1 was a direct target of miR-637, while miR-637 could drive the malignant phenotype of glioma by suppressing HMGA1 both and . Furthermore, interaction between cytoplasmic HMGA1 and vimentin was observed, and vimentin inhibition could abolish increased migration and invasion induced by HMGA1 overexpression. Both HMGA1 and vimentin were associated with an unfavorable prognosis in glioma. Additionally, upregulated HMGA1 and vimentin were found in isocitrate dehydrogenase (IDH) wild-type and 1p/19q non-codeletion diffusely infiltrating glioma. In conclusion, we identified an oncogenic ZEB2/miR-637/HMGA1 signaling axis targeting vimentin that promotes both migration and invasion in glioma.

更新日期：2021-01-05

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