TGF-β 激活的 circRYK 通过 ceRNA 和 RBP 依赖的方式增加 VLDLR mRNA 的表达和稳定性，从而促进胶质母细胞瘤的进展。

TGF-β-activated circRYK drives glioblastoma progression by increasing VLDLR mRNA expression and stability in a ceRNA- and RBP-dependent manner.

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, 210000, China.

出版信息

J Exp Clin Cancer Res. 2024 Mar 8;43(1):73. doi: 10.1186/s13046-024-03000-3.

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.

背景

TGF-β 信号通路与胶质母细胞瘤（GBM）的进展密切相关。本研究旨在探讨 circRNAs 在 TGF-β 信号通路中的作用。

方法

在我们的研究中，我们使用转录组分析来寻找受 TGF-β 激活的 circRNAs。在确认所选 circRYK 的表达模式后，我们进行了体外和体内细胞功能测定。通过 RNA 下拉、荧光素酶报告基因和 RNA 免疫沉淀测定分析了潜在机制。

结果

circRYK 在 GBM 中表达明显上调，这种表型与预后不良密切相关。功能上，circRYK 促进 GBM 中的上皮-间充质转化和 GSC 维持。在机制上，circRYK 通过 RNA 结合蛋白 HuR 海绵吸附 miR-330-5p 并促进癌基因 VLDLR 的表达。此外，circRYK 可以通过 VLDLR mRNA 的 RNA 结合蛋白 HuR 增强其稳定性。