Abstract
Increasing number of studies have proven that circular RNAs (circRNAs) play a major role in the biological processes of many different cancers, including glioma, especially as competitive molecular sponges of microRNAs (miRNAs). However, the clear molecular mechanism of the circRNA network in glioma is still not well understood. The expression level of circRNA-104718 and microRNA (miR)-218-5p in glioma tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The target protein’s expression level was assessed by western blotting. Bioinformatics systems were used to predict the possible microRNAs and target genes of circRNA-104718, after which dual-luciferase reporter assays were used to confirm the predicted interactions. The proliferation, invasion, migration and apoptosis of glioma cells were detected by CCK, EdU, transwell, wound-healing and flow cytometry assays. CircRNA-104718 was upregulated in human glioma tissues, and a higher level of circRNA-104718 indicated poorer outcomes in glioma patients. In contrast, in glioma tissues, miR-218-5p was downregulated. Knockdown of circRNA-104718 suppressed migration and invasion while boosting the apoptosis rate of glioma cells. In addition, the upregulation of miR-218-5p in glioma cells caused the same suppression. Mechanistically, circRNA-104718 inhibited the protein expression level of high mobility group box-1 (HMGB1) by acting as a molecular sponge for miR-218-5p. CircRNA-104718 is a suppressive factor in glioma cells and might represent a new target for the treatment of glioma patients. CircRNA-104718 modulates glioma cell proliferation through the miR-218-5p/HMGB1 signalling axis. CircRNA-104718 provides a possible mechanism for understanding the pathogenesis of glioma.
Highlights
CircRNA-104718 is overexpressed in human glioma.
CircRNA-104718 promotes malignant phenotypes of glioma cells.
CircRNA-104718 sponges miR-218-5p to promote glioma progression.
CircRNA-104718 targets miR-218-5p to upregulate the expression of HMGB1.
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Data Availability
The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.
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This work was supported by grants from the National Natural Science Foundation of China (81960541/82060455), the Natural Science Foundation of Gansu Province (grant nos. 21JR7RA420/21JR7RA426), the Lanzhou Science and Technology Bureau Project (2021-RC-97), Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital Grant Numbers: CY2022-QN-B05.
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Y.W.P. and G.Q.Y. designed and supervised the experiments. Y.J.Y., J.H.H., H.Y.W. and T.X.G. performed the experiments. Q.D. and H.Y. guided the operation of experiment and performed the data analysis. All authors read and approved the final manuscript.
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The present study was approved by The Medical Ethics Committee of The Second Hospital of Lanzhou University. All informed consent was obtained from the subject(s) and/or guardian(s). Registry and the Registration No:2022 A-412. Animal Studies No: D2022-259.
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Yan, Y., Wang, H., Hu, J. et al. CircRNA-104718 promotes glioma malignancy through regulation of miR-218-5p/HMGB1 signalling pathway. Metab Brain Dis 38, 1531–1542 (2023). https://doi.org/10.1007/s11011-023-01194-7
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DOI: https://doi.org/10.1007/s11011-023-01194-7