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The U2AF65/circNCAPG/RREB1 feedback loop promotes malignant phenotypes of glioma stem cells through activating the TGF-β pathway.
- Source :
-
Cell death & disease [Cell Death Dis] 2023 Jan 13; Vol. 14 (1), pp. 23. Date of Electronic Publication: 2023 Jan 13. - Publication Year :
- 2023
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Abstract
- Glioma is the most aggressive and common malignant neoplasms in human brain tumors. Numerous studies have showed that glioma stem cells (GSCs)drive the malignant progression of gliomas. Recent studies have revealed that circRNAs can maintain stemness and promote malignant progression of glioma stem cells. We used bioinformatics analysis to identify circRNAs and potential RNA-binding proteins (RBPs) in glioma. qRT-PCR, western blotting, RNA FISH, RNA pull-down, RNA immunoprecipitation assay, ChIP, immunohistochemistry, and immunofluorescence methods were used to quantified the expression of circNCAPG, U2AF65, RREB1 and TGF-β1, and the underlying mechanisms between them. MTS, EDU, neurosphere formation, limiting dilution neurosphere formation and transwell assays examined the proliferation and invasive capability of GSCs, respectively. We identified a novel circRNA named circNCAPG was overexpressed and indicated the poor prognosis in glioma patients. Upregulating circNCAPG promoted the malignant progression of GSCs. RNA binding protein U2AF65 could stabilize circNCAPG by direct binding. Mechanically, circNCAPG interacted with and stabilized RREB1, as well as stimulated RREB1 nuclear translocation to activate TGF-β1 signaling pathway. Furthermore, RREB1 transcriptionally upregulated U2AF65 expression to improve the stability of circNCAPG in GSCs, which established a feedback loop involving U2AF65, circNCAPG and RREB1. Since circRNA is more stable than mRNA and can execute its function continuously, targeting circNCAPG in glioma may be a novel promising therapeutic.<br /> (© 2023. The Author(s).)
- Subjects :
- Humans
Cell Line, Tumor
Cell Proliferation genetics
DNA-Binding Proteins metabolism
Feedback
Gene Expression Regulation, Neoplastic
Neoplastic Stem Cells metabolism
Transcription Factors metabolism
Transforming Growth Factor beta1 genetics
Transforming Growth Factor beta1 metabolism
Splicing Factor U2AF genetics
Splicing Factor U2AF metabolism
Brain Neoplasms pathology
Glioma pathology
MicroRNAs genetics
RNA, Circular genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 36635261
- Full Text :
- https://doi.org/10.1038/s41419-023-05556-y