LncRNA FOXD1-AS1 acts as a potential oncogenic biomarker in glioma

被引:39
作者
Gao, Yuan-Feng [1 ,2 ,3 ]
Liu, Jun-Yan [4 ]
Mao, Xiao-Yuan [1 ,2 ]
He, Zheng-Wen [5 ]
Zhu, Tao [1 ,2 ]
Wang, Zhi-Bin [1 ,2 ]
Li, Xi [1 ,2 ]
Yin, Ji-Ye [1 ,2 ]
Zhang, Wei [1 ,2 ]
Zhou, Hong-Hao [1 ,2 ]
Liu, Zhao-Qian [1 ,2 ]
机构
[1] Cent S Univ, Xiangya Hosp, Dept Clin Pharmacol, Changsha 410008, Hunan, Peoples R China
[2] Cent S Univ, Hunan Key Lab Pharmacogenet, Inst Clin Pharmacol, Changsha, Hunan, Peoples R China
[3] Hunan Univ Chinese Med, Dept Pharm, Hosp 1, Changsha, Hunan, Peoples R China
[4] Univ South China, Dept Orthopaed, Affiliated Hosp 1, Hengyang, Peoples R China
[5] Cent S Univ, Dept Neurosurg, Affiliated Canc Hosp, XiangYa Sch Med, Changsha, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
eIF5a; glioma; lncRNA FOXD1-AS1; lncRNAs; miR-339; 342; LONG NONCODING RNA; LUNG-CANCER PROLIFERATION; CELL; EXPRESSION; GENE; ACTIVATION; MIGRATION; INVASION; TUMORS;
D O I
10.1111/cns.13152
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Aims Altered activities of long noncoding RNAs (lncRNAs) have been associated with cancer development, and lncRNA FOXD1-AS1 (FOXD1-AS1) is the antisense transcript of the gene encoding for FOXD1, known for its role as an oncogene in several tumor types including glioma. However, the role of FOXD1-AS1 in the differentiation and progression of glioma is not well known. Methods Expression profile chip and qPCR were used to screen and identify FOXD1-AS1. Glioma cells were transfected with siRNA or eukaryotic expression vector to observe FOXD1-AS1 function in vitro and in vivo. Dual luciferase reporter gene analysis, Western blot, and ChIRP-MS were used to detect microRNAs and protein that combine with FOXD1-AS1. Results FOXD1-AS1 was upregulated and directly correlated with the glioma grade, and it was localized in both the nucleus and the cytoplasm of the glioma cell. FOXD1-AS1 silencing caused tumor suppressive effects via inhibiting cell proliferation, migration, and apoptosis, while FOXD1-AS1 overexpression resulted in opposite effects. Additionally, in vivo experiments showed that FOXD1-AS1 knockdown reduced tumor volume and weight. More importantly, mechanical studies revealed that FOXD1-AS1 targeted both miR339-5p and miR342-3p (miR339/342). Furthermore, protein eukaryotic translation initiation factor 5 subunit A (eIF5a) resulted a direct target of FOXD1-AS1. Conclusions These data indicated that FOXD1-AS1, a miR339/342 target, affected biological processes via protein eIF5a; thus, it might be considered as a new therapeutic target for glioblastoma.
引用
收藏
页码:66 / 75
页数:10
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