FXR1 promotes the malignant biological behavior of glioma cells via stabilizing MIR17HG

被引:63
作者
Cao, Shuo [1 ,2 ,3 ]
Zheng, Jian [4 ,5 ,6 ]
Liu, Xiaobai [4 ,5 ,6 ]
Liu, Yunhui [4 ,5 ,6 ]
Ruan, Xuelei [1 ,2 ,3 ]
Ma, Jun [1 ,2 ,3 ]
Liu, Libo [1 ,2 ,3 ]
Wang, Di [4 ,5 ,6 ]
Yang, Chunqing [4 ,5 ,6 ]
Cai, Heng [4 ,5 ,6 ]
Li, Zhen [4 ,5 ,6 ]
Feng, Ziyi [1 ,7 ]
Xue, Yixue [1 ,2 ,3 ]
机构
[1] China Med Univ, Sch Life Sci, Dept Neurobiol, Shenyang 110122, Liaoning, Peoples R China
[2] China Med Univ, Key Lab Cell Biol, Minist Publ Hlth China, Shenyang 110122, Liaoning, Peoples R China
[3] China Med Univ, Key Lab Med Cell Biol, Minist Educ China, Shenyang 110122, Liaoning, Peoples R China
[4] China Med Univ, Dept Neurosurg, Shengjing Hosp, Shenyang 110004, Liaoning, Peoples R China
[5] Liaoning Clin Med Res Ctr Nervous Syst Dis, Shenyang 110004, Liaoning, Peoples R China
[6] Key Lab Neurooncol Liaoning Prov, Shenyang 110004, Liaoning, Peoples R China
[7] China Med Univ, Expt Class Clin Med Discipline, Class 102, Shenyang 110122, Liaoning, Peoples R China
关键词
RNA binding proteins; FXR1; Long non-coding RNA; MIR17HG; Glioma cells; RNA-BINDING PROTEIN; MESENCHYMAL TRANSITION; TUMOR-SUPPRESSOR; CANCER; EXPRESSION; DEC1; CARCINOMA; AMPLICON; INSIGHTS; HYPOXIA;
D O I
10.1186/s13046-018-0991-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Accumulating evidence has highlighted the potential role of RNA binding proteins (RBPs) in the biological behaviors of glioblastoma cells. Herein, the expression and function of RNA binding proteins FXR1 were investigated in human glioma cells. Quantitative real-time PCR were conducted to evaluate the expression of MIR17HG and miR-346, miRNA-425-5p in glioma tissues and cells. Western blot were used to explore the expression of FXR1, TAL1 and DEC1 in glioma tissues and cells. Stable knockdown of FXR1 and MIR17HG in glioma cells were established to explore the function of FXR1, MIR17HG in glioma cells. Further, RIP and RNA pull-down assays were used to investigate the correlation between FXR1 and MIR17HG. Cell Counting Kit-8, transwell assays, and flow cytometry were used to investigate the function of FXR1 and MIR17HG in malignant biological behaviors of glioma cells. ChIP assays were employed to ascertain the correlations between TAL1 and MIR17HG. FXR1and MIR17HG were upregulated in glioma tissues and cell lines. Downregulation of FXR1 or MIR17HG resulted in inhibition of glioma cells progression. We also found that FXR1 regulates the biological behavior of glioma cells via stabilizing MIR17HG. In addition, downregulated MIR17HG increased miR-346/miR-425-5p expression and MIR17HG acted as ceRNA to sponge miR-346/miR-425-5p. TAL1 was a direct target of miR-346/miR-425-5p, and played oncogenic role in glioma cells. More importantly, TAL1 activated MIR17HG promoter and upregulated its expression, forming a feedback loop. Remarkably, FXR1 knockdown combined with inhibition of MIR17HG resulted in the smallest tumor volumes and the longest survivals of nude mice in vivo. FXR1/MIR17HG/miR-346(miR-425-5p)/TAL1/DEC1 axis plays a novel role in regulating the malignant behavior of glioma cells, which may be a new potential therapeutic strategy for glioma therapy.
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页数:22
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共 53 条
[51]   IGF2BP3 functions as a potential oncogene and is a crucial target of miR-34a in gastric carcinogenesis [J].
Zhou, Yuhang ;
Huang, Tingting ;
Siu, Ho Lam ;
Wong, Chi Chun ;
Dong, Yujuan ;
Wu, Feng ;
Zhang, Bin ;
Wu, William K. K. ;
Cheng, Alfred S. L. ;
Yu, Jun ;
To, Ka Fai ;
Kang, Wei .
MOLECULAR CANCER, 2017, 16
[52]   MiR-17-92 cluster promotes hepatocarcinogenesis [J].
Zhu, Hanqing ;
Han, Chang ;
Wu, Tong .
CARCINOGENESIS, 2015, 36 (10) :1213-1222
[53]   Long intergenic non-coding RNA 00324 promotes gastric cancer cell proliferation via binding with HuR and stabilizing FAM83B expression [J].
Zou, Zigui ;
Ma, Tianshi ;
He, Xuezhi ;
Zhou, Jinxing ;
Ma, Hongwei ;
Xie, Min ;
Liu, Yanhua ;
Lu, Die ;
Di, Shihao ;
Zhang, Zhihong .
CELL DEATH & DISEASE, 2018, 9