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.
Highlights
Glioma accounts for the great majority of primary tumors in adult central nervous systems [1]
Expression of long noncoding RNAs (lncRNAs) ZEB1-AS1 is Up-Regulated in Glioma Tissues
It was reported that lncRNA ZEB1-AS1 was greatly up-regulated in human hepatocellular carcinoma and in esophageal squamous cell carcinoma compared with matched normal tissues [19,20]
Summary
Glioma accounts for the great majority of primary tumors in adult central nervous systems [1]. It has been reported that aberrant expression of many lncRNAs is frequently observed in cancers involved in carcinogenesis and cancer progression which indicates that dysregulated lncRNAs probably could serve as novel biomarkers for early diagnosis, effective therapeutic targets, and prognosis prediction of malignant tumors. T Li and colleagues found that lncRNA ZEB1-AS1—a non-coding antisense transcript that originates from the promoters of ZEB1—was highly expressed in hepatocellular carcinoma, especially in metastatic liver tumor tissues, and related to poor outcome of HCC patients [19], with its similar role in esophageal squamous cell carcinoma (ESCC) having been observed by Wang et al [20]. Using ZEB1-AS1-specific siRNA, we further investigated the effects as well as the potential molecular mechanism of ZEB1-AS1 downregulation involved in proliferation, apoptosis, migration and invasion of U87 and U251 cells in vitro
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