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FGD5-AS1 facilitates glioblastoma progression by activation of Wnt/β-catenin signaling via regulating miR-129-5p/HNRNPK axis
被引:29
作者:
Wu, Lixin
[1
]
Zhu, Xuqiang
[1
]
Song, Zhenyu
[1
]
Guo, Mengguo
[1
]
Liang, Junxin
[1
]
Yan, Dongming
[1
]
机构:
[1] Zhengzhou Univ, Affiliated Hosp 1, Dept Neurosurg, 1 Jianshe East Rd, Zhengzhou 450052, Peoples R China
来源:
关键词:
FGD5-AS1;
Glioblastoma;
miR-129-5p;
HNRNPK;
Wnt/beta-catenin signaling;
LONG NONCODING RNAS;
NUCLEAR RIBONUCLEOPROTEIN K;
HNRNP-K;
PROLIFERATION;
CANCER;
MICRORNA-129-5P;
METASTASIS;
MECHANISMS;
ROLES;
D O I:
10.1016/j.lfs.2020.117998
中图分类号:
R-3 [医学研究方法];
R3 [基础医学];
学科分类号:
1001 ;
摘要:
Aims: Accumulating evidence elucidates the biological significance of long non-coding RNA (lncRNAs) in tumorigenesis and development. FGD5 antisense RNA 1 (FGD5-AS1) was previously revealed as an oncogene in several types of malignancies. However, the roles of FGD5-AS1 in glioblastoma (GBM) and its potential molecular mechanisms remain unclear. Materials and methods: The expression of FGD5-AS1, miR-129-5p, and heterogeneous nuclear ribonucleoprotein K (HNRNPK) mRNA were measured by qRT-PCR. Cell proliferation, invasion and apoptosis were determined by MIT, colony formation, transwell and flow cytometry assays. The protein levels of Ki-67, HNRNPK and Wnt signaling-associated genes were examined by western blot assay. The possible action mechanism of FGD5-AS1 was detected by bioinformatic tools, luciferase reporter, RIP and TOP/FOP Flash reporter assays. A nude mouse xenograft model was built to analyze the function of FGD5-AS1 in vivo. Key findings: FGD5-AS1 expression was increased in GBM tumor tissues and cells. Knockdown of FGD5-AS1 inhibited cell proliferation and invasion in vitro, and slowed tumor growth in vivo. Mechanistically, FGD5-AS1 served as a sponge of miR-129-5p to relieve its suppression on HNRNPK. Moreover, down-regulation of HNRNPK repressed cell proliferation and invasion, while enhanced apoptosis. Additionally, si-FGD5-AS1-mediated suppression of cell proliferation and invasion was obviously reversed by the decrease of miR-129-5p or restoration of HNRNPK. Furthermore, FGD5-AS1 promoted cell growth and invasion by stimulating Wnt/beta-catenin signaling via regulation of miR-129-5p/HNRNPK. Significance: FGD5-AS1 promoted GBM progression at least partly by regulating miR-129-5p/HNRNPK to activate Wnt/beta-catenin signaling, suggesting the potential of FGD5-AS1 as a candidate target to improve GBM therapy.
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页数:13
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