Abstract
BackgroundAccumulating 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.MethodsQuantitative 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.ResultsFXR1and 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.ConclusionsFXR1/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.
Highlights
Glioblastoma is neuroepithelium-derived and the most malignant form of glioma with poor prognosis [1]
U87 glioma cells and human embryonic kidney (HEK)-293 T-cells were cultured in Dulbecco’s modified Eagle medium (DMEM)/high glucose supplemented with 10% fetal bovine serum (FBS, Gibco,Carlsbad, CA, USA), U251 glioma cells were cultured in DMEM/F12 medium supplemented with 10% FBS
FXR1 was upregulated in glioma tissues and cell lines, knockdown of FXR1 inhibited the malignant biological behavior of glioma cells The expression of FXR1 in glioma tissues and cells were detected by western blot
Summary
Glioblastoma is neuroepithelium-derived and the most malignant form of glioma with poor prognosis [1]. Revealing the pathogenesis of glioblastoma and finding new effective therapeutic targets have become the focus of current research. Growing evidence indicates that RNA binding proteins (RBPs) are abnormally expressed in a variety of tumors and are involved in the progression of various human tumors [3,4,5]. The major biological functions of RBPs include regulation of the RNA stability, splicing, nuclear output and translation [6]. A recent observation indicated that FXR1 is up-regulated in colorectal cancer tissues and. Accumulating evidence has highlighted the potential role of RNA binding proteins (RBPs) in the biological behaviors of glioblastoma cells. The expression and function of RNA binding proteins FXR1 were investigated in human glioma cells
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