Oncogenic ZEB2/miR-637/HMGA1 signaling axis targeting vimentin promotes the malignant phenotype of glioma.
Oncogenic ZEB2/miR-637/HMGA1 signaling axis targeting vimentin promotes the malignant phenotype of glioma.
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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
DOI：
10.1016/j.omtn.2020.12.029
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发表时间：
2021-03-05
期刊：
影响因子：
--
通讯作者：
Song Y
中科院分区：
文献类型：
--
作者：
Zeng Y;Que T;Lin J;Zhan Z;Xu A;Wu Z;Xie C;Luo J;Ding S;Long H;Zhang X;Song Y
神经胶质瘤是中枢神经系统最常见的原发性肿瘤。我们先前证实锌指E-box binding homeobox（ZEB）2促进胶质瘤的恶性进展，而microRNA-637（miR-637）与胶质瘤的良好预后相关。本研究旨在探讨ZEB 2与miR-637在胶质瘤中的相互作用及其下游信号通路。结果显示，ZEB 2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HMGA 1是miR-637的直接靶点，而miR-637可以通过在体外和体内抑制HMGA 1来驱动胶质瘤的恶性表型。此外，观察到细胞质HMGA 1和波形蛋白之间的相互作用，波形蛋白抑制可以消除HMGA 1过表达诱导的迁移和侵袭增加。HMGA 1和波形蛋白均与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1 p/19 q非共缺失弥漫浸润性胶质瘤中发现HMGA 1和波形蛋白上调。总之，我们确定了一个致癌的ZEB 2/miR-637/HMGA 1信号轴靶向波形蛋白，促进胶质瘤的迁移和侵袭。转录因子ZEB 2可以直接与miR-637启动子区的E-box元件结合，导致miR-637靶基因之一HMGA 1的上调。此外，HMGA 1的表达增强后，可与vimentin相互作用，增强GBM细胞的迁移和侵袭能力。
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 in vitro and in vivo. 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. Transcription factor ZEB2 could directly bind to the E-box element in the miR-637 promoter region, leading to upregulation of HMGA1, one of the miR-637 target genes. Moreover, promoted HMGA1 could interact with vimentin and increase both migration and invasion capacity of GBM cells.
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影响因子：
8.8
作者：
Mineo M;Ricklefs F;Rooj AK;Lyons SM;Ivanov P;Ansari KI;Nakano I;Chiocca EA;Godlewski J;Bronisz A
通讯作者：
Bronisz A
影响因子：
--
作者：
Pegoraro S;Ros G;Piazza S;Sommaggio R;Ciani Y;Rosato A;Sgarra R;Del Sal G;Manfioletti G
通讯作者：
Manfioletti G
影响因子：
5.8
作者：
Colamaio, Marianna;Tosti, Nadia;Fusco, Alfredo
通讯作者：
Fusco, Alfredo
影响因子：
3.6
作者：
Bund, Caroline;Guergova-Kuras, Mariana;Namer, Izzie Jacques
通讯作者：
Namer, Izzie Jacques
波形蛋白的新功能：预测黑色素瘤血行转移的潜在生物标志物
DOI：
10.1186/1756-9966-29-109
发表时间：
2010-08-11
影响因子：
11.3
作者：
Li, Man;Zhang, Baogang;Zhao, Xiulan
通讯作者：
Zhao, Xiulan