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

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.

• Authors: Qiao-Li Lv, Lei Hu, Shu-Hui Chen, Bao Sun, Meng-Long Fu, Chong-Zhen Qin, Qiang Qu, Gui-Hua Wang, Chen-Jie He, Hong-Hao Zhou
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 17 Issue 9 (Aug 30 2016) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 27589728 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Cadherins
• RNA, Long Noncoding
• ZEB1 protein, human
• Zinc Finger E-box-Binding Homeobox 1
• long non-coding RNA ZEB1-AS1, human
• Cyclin D1
• CDK2 protein, human
• Cyclin-Dependent Kinase 2
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9

Topics

• Adult
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Brain Neoplasms (genetics, metabolism, pathology)
• Cadherins (genetics, metabolism)
• Carcinogenesis (genetics, metabolism)
• Cell Line, Tumor
• Cell Proliferation
• Cyclin D1 (genetics, metabolism)
• Cyclin-Dependent Kinase 2 (genetics, metabolism)
• Epithelial-Mesenchymal Transition
• Female
• G1 Phase Cell Cycle Checkpoints
• Glioma (genetics, metabolism, pathology)
• Humans
• Male
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Middle Aged
• RNA, Long Noncoding (genetics, metabolism)
• Zinc Finger E-box-Binding Homeobox 1 (genetics, metabolism)