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Int. J. Mol. Sci. 2016, 17(9), 1431; doi:10.3390/ijms17091431

A Long Noncoding RNA ZEB1-AS1 Promotes Tumorigenesis and Predicts Poor Prognosis in Glioma

1
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China
2
Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China
3
Department of Oncology, Changsha Central Hospital, Changsha 410008, China
4
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Central South University, Zhengzhou 450052, China
5
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
*
Author to whom correspondence should be addressed.
Academic Editor: Martin Pichler
Received: 7 July 2016 / Revised: 19 August 2016 / Accepted: 22 August 2016 / Published: 30 August 2016
(This article belongs to the Collection Regulation by Non-Coding RNAs)
View Full-Text   |   Download PDF [6125 KB, uploaded 30 August 2016]   |  

Abstract

Emerging studies show that long noncoding RNAs (lncRNAs) have important roles in carcinogenesis. lncRNA ZEB1 antisense 1 (ZEB1-AS1) is a novel lncRNA, whose clinical significance, biological function, and underlying mechanism remains unclear in glioma. Here, we found that ZEB1-AS1 was highly expressed in glioma tissues, being closely related to clinical stage of glioma. Moreover, patients with high ZEB1-AS1 levels had poor prognoses, with the evidence provided by multivariate Cox regression analysis indicating that ZEB1-AS1 expression could serve as an independent prognostic factor in glioma patients. Functionally, silencing of ZEB1-AS1 could significantly inhibit cell proliferation, migration, and invasion, as well as promote apoptosis. Knockdown of ZEB1-AS1 significantly induced the G0/G1 phase arrest and correspondingly decreased the percentage of S phase cells. Further analysis indicated that ZEB1-AS1 could regulate the cell cycle by inhibiting the expression of G1/S transition key regulators, such as Cyclin D1 and CDK2. Furthermore, ZEB1-AS1 functioned as an important regulator of migration and invasion via activating epithelial to mesenchymal transition (EMT) through up-regulating the expression of ZEB1, MMP2, MMP9, N-cadherin, and Integrin-β1 as well as decreasing E-cadherin levels in the metastatic progression of glioma. Additionally, forced down-regulation of ZEB1-AS1 could dramatically promote apoptosis by increasing the expression level of Bax and reducing Bcl-2 expression in glioma. Taken together, our data suggest that ZEB1-AS1 may serve as a new prognostic biomarker and therapeutic target of glioma. View Full-Text
Keywords: long non-coding RNA; lncRNA ZEB1-AS1; glioma; prognostic biomarker; epithelial-mesenchymal transition long non-coding RNA; lncRNA ZEB1-AS1; glioma; prognostic biomarker; epithelial-mesenchymal transition
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MDPI and ACS Style

Lv, Q.-L.; Hu, L.; Chen, S.-H.; Sun, B.; Fu, M.-L.; Qin, C.-Z.; Qu, Q.; Wang, G.-H.; He, C.-J.; Zhou, H.-H. A Long Noncoding RNA ZEB1-AS1 Promotes Tumorigenesis and Predicts Poor Prognosis in Glioma. Int. J. Mol. Sci. 2016, 17, 1431.

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