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Open AccessArticle

DNA Methylation Influences miRNA Expression in Gonadotroph Pituitary Tumors

1
Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
2
Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
3
Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
4
Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, 01-813 Warsaw, Poland
5
Department of Neurosurgery, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Life 2020, 10(5), 59; https://doi.org/10.3390/life10050059
Received: 31 March 2020 / Revised: 6 May 2020 / Accepted: 7 May 2020 / Published: 13 May 2020
(This article belongs to the Section Medical Research)
microRNAs are involved in pathogenesis of cancer. DNA methylation plays a role in transcription of miRNA-encoding genes and may contribute to changed miRNA expression in tumors. This issue was not investigated in pituitary neuroendocrine tumors (PitNETs) previously. DNA methylation patterns, assessed with HumanMethylation450K arrays in 34 PitNETs and five normal pituitaries, were used to determine differentially methylated CpGs located at miRNA genes. It showed aberrant methylation in regions encoding for 131 miRNAs. DNA methylation data and matched miRNA expression profiles, determined with next-generation sequencing (NGS) of small RNAs, were correlated in 15 PitNETs. This showed relationship between methylation and expression levels for 12 miRNAs. DNA methylation and expression levels of three of them (MIR145, MIR21, and MIR184) were determined in the independent group of 80 tumors with pyrosequencing and qRT-PCR and results confirmed both aberrant methylation in PitNETs and correlation between methylation and expression. Additionally, in silico target prediction was combined with analysis of established miRNA profiles and matched mRNA expression pattern, assessed with amplicon-based NGS to indicate putative target genes of epigenetically deregulated miRNAs. This study reveals aberrant DNA methylation in miRNA-encoding genes in gonadotroph PitNETs. Methylation changes affect expression level of miRNAs that regulate putative target genes with tumorigenesis-relevant functions. View Full-Text
Keywords: epigenetics; DNA methylation; microRNA; gene expression; PitNET; gonadotropinoma epigenetics; DNA methylation; microRNA; gene expression; PitNET; gonadotropinoma
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Boresowicz, J.; Kober, P.; Rusetska, N.; Maksymowicz, M.; Paziewska, A.; Dąbrowska, M.; Zeber-Lubecka, N.; Kunicki, J.; Bonicki, W.; Ostrowski, J.; Siedlecki, J.A.; Bujko, M. DNA Methylation Influences miRNA Expression in Gonadotroph Pituitary Tumors. Life 2020, 10, 59.

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