Long noncoding RNA ZEB1-AS1 promotes the tumorigenesis of glioma cancer cells by modulating the miR-200c/141-ZEB1 axis

American Journal of Translational Research

Lei Meng¹  Ruiyan Cai²  Pengju Ma³ 

[1] Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan, China;Henan Key Laboratory of Neurorestoratology, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan, China;Research Institute of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan, China

关键词: ZEB1-AS1;    miR-200c/141;    ZEB1;    glioma;    tumorigenesis;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Long noncoding RNA Zinc Finger E-box-binding homeobox 1 antisense 1 (ZEB1-AS1) reportedly participates in the tumorigenesis of various cancers. However, the clinical significance and biological functions of ZEB1-AS1 in glioma remain virtually unknown. Here, we show that ZEB1-AS1 expression was higher in glioma tissues and cell lines than in corresponding noncancerous samples and primary normal human astrocytes, respectively. The positive correlation of ZEB1-AS1 expression with the poor prognosis and progressive histological stages of glioma patients was clinically proven. In vitro assays revealed that silencing ZEB1-AS1 inhibited glioma cancer-cell growth and motility. Xenograft experiments confirmed that ZEB1-AS1 depletion attenuated tumor growth and metastasis. Dual-luciferase report assay showed that ZEB1-AS1 directly regulated microRNA-200c/141 (miR-200c/141) in glioma cells, which was confirmed by RNA immunoprecipitation assay. Furthermore, the inhibition of miR-200c/141 partially balanced the inhibition effects of cell proliferation and motility induced by ZEB1-AS1 depletion on U87 cells. Additionally, ZEB1-AS1 can regulate ZEB1 through miR-200c/141. Hence, ZEB1-AS1 directly regulated miR-200c/141 in glioma cells and relieved the inhibition of ZEB1 caused by miR-200c/141. Overall, this study revealed a novel regulatory mechanism between ZEB1-AS1 and the miR-200c/141-ZEB1 axis. The interaction between ZEB1-AS1 and miR-200c/141-ZEB1 axis was involved in the progression of glioma cells. Therefore, targeting this interaction was a promising strategy for glioma treatment.

【 授权许可】

CC BY-NC