lncRNA ZEB1-AS1 promotes migration and metastasis of bladder cancer cells by post-transcriptional activation of ZEB1

被引:40
作者
Zhao, Xin [1 ,2 ]
Wang, Dongwen [3 ]
Ding, Yongxue [4 ]
Zhou, Jingmin [1 ,2 ]
Liu, Guanghua [1 ,2 ]
Ji, Zhigang [1 ,2 ]
机构
[1] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Urol, 1 Shuaifuyuan St, Beijing 100730, Peoples R China
[2] Peking Union Med Coll, 1 Shuaifuyuan St, Beijing 100730, Peoples R China
[3] Shanxi Med Univ, Hosp 1, Dept Urol, Taiyuan 030001, Shanxi, Peoples R China
[4] Liaoyang City Cent Hosp, Dept Urol, Liaoyang 111000, Liaoning, Peoples R China
关键词
bladder cancer; heterogenous nuclear ribonucleoprotein D0; zinc finger E-box-binding homeobox 1; zinc finger E-box-binding homeobox 1-antisense 1; metastasis; NONCODING RNA ZEB1-AS1; REGULATES PROLIFERATION; CARCINOMA; PROGRESSION; MECHANISMS; EXPRESSION; INVASION; HOTAIR; CERNA;
D O I
10.3892/ijmm.2019.4187
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The prognosis for patients with metastatic bladder cancer (BCa) is poor, and has not been improved by current treatment methods. Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumors, including bladder cancer. However, the role of zinc finger E-box-binding homeobox 1-antisense 1 (ZEB1-AS1) in BCa progression and metastasis remains unclear. The present study determined the expression level of ZEB1-AS1 in BCa and additionally investigated the functional role of ZEB1-AS1 in BCa metastasis. Reverse transcription quantitative polymerase chain reaction analysis showed that ZEB1-AS1 was upregulated in BCa cells compared with normal epithelial cells. Functionally, knockdown of ZEB1-AS1 suppressed BCa cell migration and invasion in vitro, and metastasis in vivo. Mechanistic investigations revealed that ZEB1-AS1 bound to heterogenous nuclear ribonucleoprotein D0 (AUF1), thereby activating the translation of ZEB1 mRNA without affecting its mRNA level. In addition, ZEB1-AS1 was significantly upregulated in BCa tissues and muscle-invasive BCa cases. ROC curve analysis demonstrated that ZEB1-AS1 expression was associated with metastasis in patients with BCa. In conclusion, the data from the present study demonstrated that ZEB1-AS1 induced BCa metastasis via an AUF1-mediated translation activation of ZEB1 mRNA mechanism. ZEB1-AS1 may serve as a promising target for clinical intervention in advanced BCa.
引用
收藏
页码:196 / 206
页数:11
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