Expression and Functional Role of Reprogramming-Related Long Noncoding RNA (lincRNA-ROR) in Glioma

被引:77
作者
Feng, Shiyu [1 ]
Yao, Jie [2 ]
Chen, Yang [3 ]
Geng, Peiliang [3 ]
Zhang, Haibo [1 ]
Ma, Xiaodong [1 ]
Zhao, Jing [4 ]
Yu, Xinguang [1 ]
机构
[1] Chinese Peoples Liberat Army Gen Hosp, Dept Neurosurg, Beijing 100853, Peoples R China
[2] 161st Hosp PLA, Dept Oncol, Wuhan 430010, Peoples R China
[3] Chinese Peoples Liberat Army Gen Hosp, Div Internal Med, Beijing 100853, Peoples R China
[4] Hebei United Univ, Dept Pathol, Tangshan 63000, Peoples R China
关键词
LncRNA; LincRNA-ROR; Glioma; Glioma stem cells; KLF4; STEM-CELLS; CANCER; LINKS; KLF4;
D O I
10.1007/s12031-014-0488-z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The objective of the study was to investigate the expression and function of reprogramming-related long noncoding RNA (lincRNA-ROR) in glioma and glioma stem cells (GSCs). With real-time quantitative PCR, we analyzed lincRNA-ROR expression levels in 26 primary glioma patients and the expression correlation of lincRNA-ROR with SOX11 and KLF4. To explore its functional role, gain- and loss-of-function studies were performed to assess the effect of lincRNA-ROR on cell proliferation, expression rate of GSCs marker CD133, and glioma stem sphere-forming ability in vitro. We found that the lincRNA-ROR expression was significantly lower in glioma tissues than in adjacent normal tissues. Knockdown of lincRNA-ROR expression by small hairpin RNA (shRNA) significantly elevated the cell proliferation and enhanced the CD133 expression rate and glioma stem sphere-forming ability in U87 cells, while overexpression of lincRNA-ROR in U87 cells showed the opposite effect. Moreover, we found that the expression of lincRNA-ROR was negatively correlated with stem cell factor KLF4 and the "up- and down-regulation" of lincRNA-ROR resulted in inverse modulation of KLF4 messenger RNA (mRNA) expression. Our results suggest that the reprogramming-related lincRNA-ROR may serve as a novel tumor suppressor gene in glioma, which can inhibit the proliferation of cancer cell and self-renewal of GSCs, partly by inhibiting the KLF4 expression. Further research about lincRNA-ROR may provide a novel biomarker and therapeutic target of glioma for cancer clinic in future.
引用
收藏
页码:623 / 630
页数:8
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