title: 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: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. lvqiaoli2008@126.com.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. lvqiaoli2008@126.com.
authors: Qiao-Li
authors: QL
authors: Lv
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. hu773589905@163.com.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. hu773589905@163.com.
authors: Lei
authors: L
authors: Hu
authors: Department of Oncology, Changsha Central Hospital, Changsha 410008, China. chenshuhui2008@126.com.
authors: Shu-Hui
authors: SH
authors: Chen
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. scy_csu2016@163.com.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. scy_csu2016@163.com.
authors: Bao
authors: B
authors: Sun
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. m13397602527@163.com.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. m13397602527@163.com.
authors: Meng-Long
authors: ML
authors: Fu
authors: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Central South University, Zhengzhou 450052, China. qcz0378@126.com.
authors: Chong-Zhen
authors: CZ
authors: Qin
authors: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China. quqiang1983@sina.com.
authors: Qiang
authors: Q
authors: Qu
authors: Department of Oncology, Changsha Central Hospital, Changsha 410008, China. zhuifenglang12@126.com.
authors: Gui-Hua
authors: GH
authors: Wang
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. hechenjie1307@163.com.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. hechenjie1307@163.com.
authors: Chen-Jie
authors: CJ
authors: He
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. hhzhou2003@126.com.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. hhzhou2003@126.com.
authors: Hong-Hao
authors: HH
authors: Zhou
mesh_terms: D000328:Adult; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D062085:RNA, Long Noncoding; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; C000610978:long non-coding RNA ZEB1-AS1, human; D019938:Cyclin D1; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: epithelial-mesenchymal transition; glioma; lncRNA ZEB1-AS1; long non-coding RNA; prognostic biomarker