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Updated: Jul 1, 2025
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
TGF-β-activated circRYK drives glioblastoma progression by increasing VLDLR mRNA expression and stability in a ceRNA-
Yuhang Wang1, Binbin Wang1, Wenping Cao2
1Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, 210000, China.
Background:
The TGF-β signalling pathway is intricately associated with the progression of glioblastoma (GBM). The objective of this study was to examine the role of circRNAs in the TGF-β signalling pathway.
Methods:
In our research, we used transcriptome analysis to search for circRNAs that were activated by TGF-β. After confirming the expression pattern of the selected circRYK, we carried out in vitro and in vivo cell function assays. The underlying mechanisms were analysed via RNA pull-down, luciferase reporter, and RNA immunoprecipitation assays.
Results:
CircRYK expression was markedly elevated in GBM, and this phenotype was strongly associated with a poor prognosis. Functionally, circRYK promotes epithelial-mesenchymal transition and GSC maintenance in GBM. Mechanistically, circRYK sponges miR-330-5p and promotes the expression of the oncogene VLDLR. In addition, circRYK could enhance the stability of VLDLR mRNA via the RNA-binding protein HuR.
Conclusion:
Our findings show that TGF-β promotes epithelial-mesenchymal transition and GSC maintenance in GBM through the circRYK-VLDLR axis, which may provide a new therapeutic target for the treatment of GBM.
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