A proof-of-concept study for the pathogenetic role of enhancer hypomethylation of MYBPHL in multiple myeloma

Abstract Enhancer DNA methylation and expression of MYBPHL was studied in multiple myeloma (MM). By bisulfite genomic sequencing, among the three CpGs inside the MYBPHL enhancer, CpG1 was significantly hypomethylated in MM cell lines (6.7–50.0%) than normal plasma cells (37.5–75.0%) (P = 0.007), whi...

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Autores principales:	Kwan Yeung Wong, Gareth J. Morgan, Eileen M. Boyle, Alfred Sze Lok Cheng, Kevin Yuk-Lap Yip, Chor Sang Chim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d58c3083d67245f89af33385adaad2f0
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spelling	oai:doaj.org-article:d58c3083d67245f89af33385adaad2f02021-12-02T13:24:14ZA proof-of-concept study for the pathogenetic role of enhancer hypomethylation of MYBPHL in multiple myeloma10.1038/s41598-021-86473-y2045-2322https://doaj.org/article/d58c3083d67245f89af33385adaad2f02021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86473-yhttps://doaj.org/toc/2045-2322Abstract Enhancer DNA methylation and expression of MYBPHL was studied in multiple myeloma (MM). By bisulfite genomic sequencing, among the three CpGs inside the MYBPHL enhancer, CpG1 was significantly hypomethylated in MM cell lines (6.7–50.0%) than normal plasma cells (37.5–75.0%) (P = 0.007), which was negatively correlated with qPCR-measured MYBPHL expression. In RPMI-8226 and WL-2 cells, bearing the highest CpG1 methylation, 5-azadC caused enhancer demethylation and expression of MYBPHL. In primary samples, higher CpG1 methylation was associated with lower MYBPHL expression. By luciferase assay, luciferase activity was enhanced by MYBPHL enhancer compared with empty vector control, but reduced by site-directed mutagenesis of each CpG. RNA-seq data of newly diagnosed MM patients showed that MYBPHL expression was associated with t(11;14). MOLP-8 cells carrying t(11;14) express the highest levels of MYBPHL, and its knockdown reduced cellular proliferation and increased cell death. Herein, as a proof-of-concept, our data demonstrated that the MYBPHL enhancer, particularly CpG1, was hypomethylated and associated with increased MYBPHL expression in MM, which was implicated in myelomagenesis.Kwan Yeung WongGareth J. MorganEileen M. BoyleAlfred Sze Lok ChengKevin Yuk-Lap YipChor Sang ChimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kwan Yeung Wong Gareth J. Morgan Eileen M. Boyle Alfred Sze Lok Cheng Kevin Yuk-Lap Yip Chor Sang Chim A proof-of-concept study for the pathogenetic role of enhancer hypomethylation of MYBPHL in multiple myeloma
description	Abstract Enhancer DNA methylation and expression of MYBPHL was studied in multiple myeloma (MM). By bisulfite genomic sequencing, among the three CpGs inside the MYBPHL enhancer, CpG1 was significantly hypomethylated in MM cell lines (6.7–50.0%) than normal plasma cells (37.5–75.0%) (P = 0.007), which was negatively correlated with qPCR-measured MYBPHL expression. In RPMI-8226 and WL-2 cells, bearing the highest CpG1 methylation, 5-azadC caused enhancer demethylation and expression of MYBPHL. In primary samples, higher CpG1 methylation was associated with lower MYBPHL expression. By luciferase assay, luciferase activity was enhanced by MYBPHL enhancer compared with empty vector control, but reduced by site-directed mutagenesis of each CpG. RNA-seq data of newly diagnosed MM patients showed that MYBPHL expression was associated with t(11;14). MOLP-8 cells carrying t(11;14) express the highest levels of MYBPHL, and its knockdown reduced cellular proliferation and increased cell death. Herein, as a proof-of-concept, our data demonstrated that the MYBPHL enhancer, particularly CpG1, was hypomethylated and associated with increased MYBPHL expression in MM, which was implicated in myelomagenesis.
format	article
author	Kwan Yeung Wong Gareth J. Morgan Eileen M. Boyle Alfred Sze Lok Cheng Kevin Yuk-Lap Yip Chor Sang Chim
author_facet	Kwan Yeung Wong Gareth J. Morgan Eileen M. Boyle Alfred Sze Lok Cheng Kevin Yuk-Lap Yip Chor Sang Chim
author_sort	Kwan Yeung Wong
title	A proof-of-concept study for the pathogenetic role of enhancer hypomethylation of MYBPHL in multiple myeloma
title_short	A proof-of-concept study for the pathogenetic role of enhancer hypomethylation of MYBPHL in multiple myeloma
title_full	A proof-of-concept study for the pathogenetic role of enhancer hypomethylation of MYBPHL in multiple myeloma
title_fullStr	A proof-of-concept study for the pathogenetic role of enhancer hypomethylation of MYBPHL in multiple myeloma
title_full_unstemmed	A proof-of-concept study for the pathogenetic role of enhancer hypomethylation of MYBPHL in multiple myeloma
title_sort	proof-of-concept study for the pathogenetic role of enhancer hypomethylation of mybphl in multiple myeloma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d58c3083d67245f89af33385adaad2f0
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A proof-of-concept study for the pathogenetic role of enhancer hypomethylation of MYBPHL in multiple myeloma

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