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m6A RNA modification and its writer/reader VIRMA/YTHDF3 in testicular germ cell tumors: a role in seminoma phenotype maintenance

m6A RNA modification and its writer/reader VIRMA/YTHDF3 in testicular germ cell tumors: a role in seminoma phenotype maintenance

Authors :
João Lobo
Ana Laura Costa
Mariana Cantante
Rita Guimarães
Paula Lopes
Luís Antunes
Isaac Braga
Jorge Oliveira
Mattia Pelizzola
Rui Henrique
Carmen Jerónimo
Source :
Journal of Translational Medicine, Vol 17, Iss 1, Pp 1-13 (2019)
Publication Year :
2019
Publisher :
BMC, 2019.

Abstract

Abstract Background Covalent RNA modifications, such as N-6-methyladenosine (m6A), have been associated with various biological processes, but their role in cancer remains largely unexplored. m6A dynamics depends on specific enzymes whose deregulation may also impact in tumorigenesis. Herein, we assessed the differential abundance of m6A, its writer VIRMA and its reader YTHDF3, in testicular germ cell tumors (TGCTs), looking for clinicopathological correlates. Methods In silico analysis of TCGA data disclosed altered expression of VIRMA (52%) and YTHDF3 (48%), prompting subsequent validation. Formalin-fixed paraffin-embedded tissues from 122 TGCTs (2005–2016) were selected. RNA extraction, cDNA synthesis and real-time qPCR (Taqman assays) for VIRMA and YTHDF3 were performed, as well as immunohistochemistry for VIRMA, YTHDF3 and m6A, for staining intensity assessment. Associations between categorical variables were assessed using Chi square and Fisher’s exact test. Distribution of continuous variables between groups was compared using the nonparametric Mann–Whitney and Kruskal–Wallis tests. Biomarker performance was assessed through receiver operating characteristics (ROC) curve construction and a cut-off was established by Youden’s index method. Statistical significance was set at p

Details

Language :
English
ISSN :
14795876
Volume :
17
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal of Translational Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.186c0002fac045c6a5593860d264ebd1
Document Type :
article
Full Text :
https://doi.org/10.1186/s12967-019-1837-z