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
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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共 41 条
[1]   Emerging roles of heterogeneous nuclear ribonucleoprotein K (hnRNP K) in cancer progression [J].
Barboro, Paola ;
Ferrari, Nicoletta ;
Balbi, Cecilia .
CANCER LETTERS, 2014, 352 (02) :152-159
[2]   Long noncoding RNAs in cancer: mechanisms of action and technological advancements [J].
Bartonicek, Nenad ;
Maag, Jesper L. V. ;
Dinger, Marcel E. .
MOLECULAR CANCER, 2016, 15
[3]   Long Noncoding RNA and Cancer: A New Paradigm [J].
Bhan, Arunoday ;
Soleimani, Milad ;
Mandal, Subhrangsu S. .
CANCER RESEARCH, 2017, 77 (15) :3965-3981
[4]   Current and future strategies for treatment of glioma [J].
Bush, Nancy Ann Oberheim ;
Chang, Susan M. ;
Berger, Mitchel S. .
NEUROSURGICAL REVIEW, 2017, 40 (01) :1-14
[5]   Heterogeneous nuclear ribonucleoprotein K is associated with poor prognosis and regulates proliferation and apoptosis in bladder cancer [J].
Chen, Xu ;
Gu, Peng ;
Xie, Ruihui ;
Han, Jinli ;
Liu, Hao ;
Wang, Bo ;
Xie, Weibin ;
Xie, Weijie ;
Zhong, Guangzheng ;
Chen, Changhao ;
Xie, Shujie ;
Jiang, Ning ;
Lin, Tianxin ;
Huang, Jian .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2017, 21 (07) :1266-1279
[6]   Survival in glioblastoma: a review on the impact of treatment modalities [J].
Delgado-Lopez, P. D. ;
Corrales-Garcia, E. M. .
CLINICAL & TRANSLATIONAL ONCOLOGY, 2016, 18 (11) :1062-1071
[7]   MiR-129-5p inhibits glioma cell progression in vitro and in vivo by targeting TGIF2 [J].
Diao, Yuling ;
Jin, Baozhe ;
Huang, Liyong ;
Zhou, Wenke .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2018, 22 (04) :2357-2367
[8]   The Path Toward PET-Guided Radiation Therapy for Glioblastoma in Laboratory Animals: A Mini Review [J].
Donche, Sam ;
Verhoeven, Jeroen ;
Descamps, Benedicte ;
Bolcaen, Julie ;
Deblaere, Karel ;
Boterberg, Tom ;
Van den Broecke, Caroline ;
Vanhove, Christian ;
Goethals, Ingeborg .
FRONTIERS IN MEDICINE, 2019, 6
[9]   Long non-coding RNA FGD5-AS1 promotes non-small cell lung cancer cell proliferation through sponging hsa-miR-107 to up-regulate FGFRL1 [J].
Fan, Yafeng ;
Li, Hongxia ;
Yu, Zhongping ;
Dong, Wen ;
Cui, Xiaoyan ;
Ma, Jinlian ;
Li, Shengwen .
BIOSCIENCE REPORTS, 2020, 40
[10]   Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer [J].
Fang, Yiwen ;
Fullwood, Melissa J. .
GENOMICS PROTEOMICS & BIOINFORMATICS, 2016, 14 (01) :42-54