1. A novel promoter-associated non-coding small RNA paGLI1 recruits FUS/P65 to transactivate GLI1 gene expression and promotes infiltrating glioma progression.
- Author
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Zhong J, Xu M, Su Z, Zhang M, Yu T, Nie L, Gong J, Chen X, Chen N, and Zhou Q
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cell Line, Tumor, Cell Proliferation genetics, Child, Child, Preschool, Female, Gene Expression Regulation, Neoplastic genetics, Humans, Infant, Male, Middle Aged, Oncogenes genetics, PC-3 Cells, Signal Transduction genetics, Young Adult, Gene Expression genetics, Glioma genetics, Promoter Regions, Genetic genetics, RNA, Untranslated genetics, RNA-Binding Protein FUS genetics, Transcription Factor RelA genetics, Zinc Finger Protein GLI1 genetics
- Abstract
Glioma-associated oncogene homolog 1 (GLI1) is a core component of the Hedgehog (HH) signalling pathway and is a transcription activator of numerous oncogenes, such as SOX9, VEGFA, BCL2, and CDK2. The complex regulation of GLI1 involves numerous pathways and molecules, including HH-dependent and independent, epigenetic and post-transcriptional mechanisms. Here, we report the discovery, characterization and function of a novel sense promoter-associated ncRNA, paGLI1 that is overexpressed in infiltrating glioma. We show that paGLI1 promotes GLI1 gene transcription through binding to and recruitment of the transcription factor complex FUS/P65 by interacting with paGLI1 DNA sequence. This interaction facilitates FUS/P65 binding to the GLI1 promoter to activate GLI1 transcription and hence its downstream oncogenes, which results in enhancement of glioma cell proliferation and invasiveness. Importantly, over-expression of paGLI1 is a significant unfavorable prognosticator for both disease-specific and progression-free survival in glioma patients, with relative risks being 2.932 (95% confidence interval: 1.280 to 6.713) (P < 0.05) and 2.284 (95% confidence interval: 1.051 to 4.966) (P < 0.05), respectively. The novel paGLI1/FUS/P65 regulatory mechanisms play important roles in infiltrating glioma progression and may serve as potential targets for future therapeutics., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
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