Circular RNA circ_0001588 sponges miR‐211‐5p to facilitate the progression of glioblastoma via up‐regulating YY1 expression

Abstract

Background As the most common and detrimental brain tumor with high invasiveness and poor prognosis, glioblastoma (GBM) has severely threatened people's health globally. Therefore, it is of great importance and necessary to identify the molecular mechanisms involved in tumorigenesis and development, thus contributing to potential therapeutic targets and strategies. Methods The level of circ_0001588 was detected in 68 pairs of GBM tissues and adjacent normal tissues and human glioma cell lines via a real‐time quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR). Then, the effect of circ_0001588 on the proliferation, migration and invasion of glioma cells was evaluated. In addition, potential downstream targets of circ_0001588 were forecasted by circBANK and Starbase. Their interaction was confirmed by introducing luciferase reporter assays. Moreover, sh‐circ_0001588 transfected U251 cells were used to form tumors in vivo. Finally, the functional mechanism of circ_0001588 was identified by qRT‐PCR, western blotting, xenograft and immunohistochemistry (IHC) assays. Results The expression of circ_0001588 is markedly up‐regulated in GBM tissues and human gliomas cells. Additionally, increased expression of circ_0001588 is positively relevant with poor survival in GBM patients. The down‐regulation of circ_0001588 distinctly inhibits the proliferation, migration and invasion of GBM in vitro, as well as tumor growth in vivo. Moreover, knockdown of circ_0001588 reduces the tumor volume and weight, enhances the relative IHC staining index of E‐cadherin and decreases the relative IHC staining index of Ki‐67, Yin Yang 1 (YY1) and vinmentin in vivo. Mechanistically, circ_0001588 locates in the cytoplasm, which is directly bound with miR‐211‐5p. Furthermore, circ_0001588 can positively regulate YY1 via sponging miR‐211‐5p. Moreover, circ_0001588 accelerates the proliferation, migration and invasion of GBM by modulating miR‐211‐5p/YY1 signaling. Conclusions These results illustrate a new circ_0001588/miR‐211‐5p/YY1 regulatory signaling axis in GBM.

circRPPH1_025 Overexpression Promotes Migration and Invasion of Glioblastoma Multiforme

“…After 14 days of culture, removing the previous medium, cells were fixed with 4% paraformaldehyde, and then, cells were stained with 0.1% crystal violet. Cell colonies > 50 cells were counted under the microscope, and the colony formation rate was calculated [ 20 ].…”

Research Progress of circRNAs in Glioblastoma

“…Mucin (MUC) acts as an inducer to activate various signaling pathways that also contribute to EMT ( Ponnusamy et al, 2013 ). We found that among the circRNAs involved in GBM, circ-MMP9( Wang et al, 2018b ), hsa_circ_0067934 ( Xin et al, 2019 ), hsa_circ_0001801 ( Chen et al, 2019 ), circ-PARP4 ( Zhou J. et al, 2021 ), circ-PITX1 ( Cao et al, 2021 ), hsa_circ_0006168 ( Wang T. et al, 2021 ), hsa_circ_0001588 ( Wang Q. et al, 2021 ) and circ-MELK ( Zhou F. et al, 2021 ) can regulate GBM invasion and metastasis by modulating the EMT process. Hsa_circ_0067934 ( Xin et al, 2019 ), circ-EPB41L5 ( Lv et al, 2020 ) and circ-ABCC3( Zhang and Xu, 2021 ) can participate in the invasion and metastasis of GBM by regulating the PI3K/Akt/mtor signaling pathway.…”

“…Wang et al, Found that hsa_circ_0006168 may promote tumor growth in GBM by acting as a competitive endogenous RNA for miR-628-5p and regulating the IGF1R/Ras/Erk pathway ( Wang T. et al, 2021 ). Circ_0001588 may promote the proliferative capacity of GBM cells by regulating the miR-211-5p/YY1 signaling pathway ( Wang Q. et al, 2021 ).…”

“…CircRNAs have vital roles in the invasion and metastasis of GBM. Hsa_circ_0008344 ( Zhou et al, 2018 ), circ-MMP9( Wang et al, 2018b ), hsa_circ_0029426 ( Zhang G. et al, 2019 ), hsa_circ_0074027 ( Qian et al, 2019 ), hsa_circ_0067934 ( Xin et al, 2019 ), circ-FOXO3 ( Zhang S. et al, 2019 ), hsa_circ_0001801 ( Chen et al, 2019 ), circ-EPB41L5 ( Lv et al, 2020 ), circ-ENTPD7 ( Zhu et al, 2020 ), hsa_circ_0043278 ( Wu et al, 2020 ), circ-PARP4 ( Zhou J. et al, 2021 ), circ-SMARCA5 ( Barbagallo et al, 2021 ), circ-PITX1 ( Cao et al, 2021 ), circ-ABCC3( Zhang and Xu, 2021 ), hsa_circ_0006168 ( Wang T. et al, 2021 ), hsa_circ_0001588 ( Wang Q. et al, 2021 ), circ-MELK ( Zhou F. et al, 2021 ), circ-FLN1 ( Sun et al, 2021 ), circ-LGMN( Chen B. et al, 2021 ), circ-NT5E ( Wang et al, 2018a ), hsa_circ_0001946 ( Li and Diao, 2019 ) and circ-MTO1 ( Zhang X. et al, 2019 ) are involved in the regulation of GBM invasion and metastasis ( Table 2 ).…”

“…To further analyze the prognostic value of circRNAs in GBM, we evaluated the association of circRNAs expression levels with the overall survival (OS) rate of GBM patients. Twelve upregulated circRNAs were reported to predict poorer OS in GBM patients ( Zhang G. et al, 2019 ; Qian et al, 2019 ; Xin et al, 2019 ; Zhu et al, 2020 ; Chen B. et al, 2021 ; Li D. et al, 2021 ; Liu L. et al, 2021 ; Wang Q. et al, 2021 ; Wu X. et al, 2021 ; Zhou M. et al, 2021 ; Sun et al, 2021 ), and three downregulated circRNAs predicted poorer OS in GBM patients ( Zhang X. et al, 2019 ; Lv et al, 2020 ; Wang T. et al, 2021 ). It was shown that lower expression of has_circ_0067934 was associated with longer disease-free survival (DFS) ( Xin et al, 2019 ).…”