The VIM-AS1/miR-655/ZEB1 axis modulates bladder cancer cell metastasis by regulating epithelial-mesenchymal transition.

The VIM-AS1/miR-655/ZEB1 axis modulates bladder cancer cell metastasis by regulating epithelial-mesenchymal transition.
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DOI:
10.1186/s12935-021-01841-y
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发表时间:
2021-04-26
影响因子:
5.8
通讯作者:
Qi L
Qi L
中科院分区:
医学2区
文献类型:
--
作者:
Xiong Y;Zu X;Wang L;Li Y;Chen M;He W;Qi L

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侵袭性膀胱肿瘤导致患者预后不良,仍然是临床挑战。上皮间质转化(EMT)与膀胱癌转移有关。在本研究中,我们试图证明一种新的机制,通过这种机制,长非编码RNA(lncRNA)-miRNA-mRNA轴调节膀胱癌的EMT和转移。免疫荧光(IF)染色检测Vimentin的表达。采用免疫印迹法检测ZEB 1、波形蛋白、E-钙粘蛋白和Snail蛋白的表达。采用Transwell法检测膀胱癌细胞的侵袭能力。使用伤口愈合测定来测量膀胱癌细胞的迁移能力。本文中,我们鉴定lncRNA VIM-AS 1为膀胱癌中,特别是转移性膀胱癌组织和高转移性膀胱癌细胞系中高度表达的lncRNA。通过充当miR-655的ceRNA,VIM-AS 1与ZEB 1竞争miR-655结合,从而消除miR-655介导的ZEB 1抑制,最终促进高转移性和低转移性膀胱癌细胞中的EMT并增强癌细胞转移。总之,VIM-AS 1/miR-655/ZEB 1轴可能是通过EMT相关机制改善膀胱癌转移的有希望的靶点。
Invasive bladder tumors cause a worse prognosis in patients and remain a clinical challenge. Epithelial–mesenchymal transition (EMT) is associated with bladder cancer metastasis. In the present research, we attempted to demonstrate a novel mechanism by which a long noncoding RNA (lncRNA)-miRNA-mRNA axis regulates EMT and metastasis in bladder cancer. Immunofluorescence (IF) staining was used to detect Vimentin expression. The protein expression of ZEB1, Vimentin, E-cadherin, and Snail was investigated by using immunoblotting assays. Transwell assays were performed to detect the invasive capacity of bladder cancer cells. A wound healing assay was used to measure the migratory capacity of bladder cancer cells. Herein, we identified lncRNA VIM-AS1 as a highly- expressed lncRNA in bladder cancer, especially in metastatic bladder cancer tissues and high-metastatic bladder cancer cell lines. By acting as a ceRNA for miR-655, VIM-AS1 competed with ZEB1 for miR-655 binding, therefore eliminating the miR-655-mediated suppression of ZEB1, finally promoting EMT in both high- and low-metastatic bladder cancer cells and enhancing cancer cell metastasis. In conclusion, the VIM-AS1/miR-655/ZEB1 axis might be a promising target for improving bladder cancer metastasis via an EMT-related mechanism.
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