RNA m6a Methylation Regulator Expression in Castration-Resistant Prostate Cancer Progression and Its Genetic Associations
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Description
N6-methyladenosine (m6A) methylation, a prevalent epitranscriptomic modification, plays a crucial role in regulating mRNA expression, stability, and translation in mammals. M6A regulators have gained attention for their potential implications in tumorigenesis and clinical applications, such as cancer diagnosis and therapeutics. The existing literature predominantly addresses m6A regulators in the context of primary prostate cancer (PCa). However, a notable gap in the knowledge emerges regarding the dynamic expression patterns of these regulators as PCa progresses towards the castration-resistant stage (CRPC). Employing sequential window acquisition of all theoretical mass spectra (SWATH-MS) and RNAseq analysis, we comprehensively profiled the expression of 27 m6A regulators in hormone/androgen-dependent and -independent PCa cell lines, revealing distinct clustering between tumor and adjacent normal prostate tissues. High-grade PCa tumors demonstrated the upregulation of METTL3, RBM15B, and HNRNAPA2B1 and the downregulation of ZC3H13, NUDT21, and FTO. Notably, we identified six m6A regulators associated with PCa survival. Additionally, association analysis of the PCa-associated risk loci in the cancer genome atlas program (TCGA) data unveiled genetic variations near the WTAP, HNRNPA2B1, and FTO genes as significant expression quantitative trait loci. In summary, our study unraveled abnormalities in m6A regulator expression in PCa progression, elucidating their association with PCa risk loci. Considering the heterogeneity within the PCa phenotypes and treatment responses, our findings suggest that prognostic stratification based on m6A regulator expression could enhance PCa diagnosis and prognosis.
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ID Code: | 249357 | ||||||
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Item Type: | Contribution to Journal (Journal Article) | ||||||
Refereed: | Yes | ||||||
ORCID iD: |
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Measurements or Duration: | 18 pages | ||||||
Keywords: | androgen-targeted therapy, castration-resistant prostate cancer, m6A methylation, prostate cancer, single-nucleotide polymorphisms | ||||||
DOI: | 10.3390/cancers16071303 | ||||||
ISSN: | 2072-6694 | ||||||
Pure ID: | 172124711 | ||||||
Divisions: | Current > Research Centres > Centre for Genomics and Personalised Health Current > QUT Faculties and Divisions > Faculty of Health Current > Schools > School of Biomedical Sciences |
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Funding Information: | This work was supported by an Advance Queensland Industry Research Fellowship AQIRF175-2019RD2, an MTPConnect REDI Fellowship, and a DoD Ideas development grant (W81XWH-19-1-0343) to J.B. | ||||||
Copyright Owner: | 2024 The Authors | ||||||
Copyright Statement: | This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au | ||||||
Deposited On: | 01 Jul 2024 23:55 | ||||||
Last Modified: | 02 Jul 2024 21:02 |
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