MiR-21, miR-34a, miR-125b, miR-181d and miR-648 levels inversely correlate with MGMT and TP53 expression in primary glioblastoma patients

Introduction TP53 and MGMT alterations play a crucial role in glioblastoma (GB) pathogenesis. TP53 and MGMT function is affected by several pathologic mechanisms, such as point mutations or promoter methylation, which are well characterized. Expression of both genes can be regulated by other mechani...

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Autores principales: Dorota Jesionek-Kupnicka, Marcin Braun, Berenika Trąbska-Kluch, Joanna Czech, Małgorzata Szybka, Bożena Szymańska, Dominika Kulczycka-Wojdala, Michał Bieńkowski, Radzisław Kordek, Izabela Zawlik
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Publicado: Termedia Publishing House 2019
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spelling oai:doaj.org-article:9878f2c77af748089cded2e35d56be052021-12-02T19:15:42ZMiR-21, miR-34a, miR-125b, miR-181d and miR-648 levels inversely correlate with MGMT and TP53 expression in primary glioblastoma patients1734-19221896-915110.5114/aoms.2017.69374https://doaj.org/article/9878f2c77af748089cded2e35d56be052019-03-01T00:00:00Zhttps://www.archivesofmedicalscience.com/MiR-21-miR-34a-miR-125b-miR-181d-and-miR-648-levels-inversely-correlate-with-MGMT,69743,0,2.htmlhttps://doaj.org/toc/1734-1922https://doaj.org/toc/1896-9151Introduction TP53 and MGMT alterations play a crucial role in glioblastoma (GB) pathogenesis. TP53 and MGMT function is affected by several pathologic mechanisms, such as point mutations or promoter methylation, which are well characterized. Expression of both genes can be regulated by other mechanisms as well, e.g., microRNAs (miRNAs). Moreover, cross-talk among various pathologic processes may occur, further affecting MGMT and TP53 functionality. Material and methods In 49 GB patients, we analyzed the possible associations between TP53 and its miRNA regulators miR-125b, miR-21, and miR-34a, as well as MGMT and its miRNA regulators miR-181d and miR-648. We evaluated the possible influence of mutational and methylation status on the pre-identified associations. Results In patients with immunohistochemistry-detected TP53 overexpression, expression levels of miR-34a and TP53 were negatively correlated (r = –0.56, p = 0.0195), and in patients with TP53 mutations, expression levels of TP53 and miR-21 were negatively correlated (r = –0.67, p = 0.0330). In patients with MGMT methylation, expression levels of MGMT were negatively correlated with miR-648 and miR-125b expression levels (r = –0.61, p = 0.0269 and r = –0.34, p = 0.0727, respectively). Conclusions Our findings demonstrate that selected miRNAs are significantly correlated with MGMT and TP53 levels, but the extent of this correlation differs regarding the TP53 and MGMT mutational and promoter methylation status.Dorota Jesionek-KupnickaMarcin BraunBerenika Trąbska-KluchJoanna CzechMałgorzata SzybkaBożena SzymańskaDominika Kulczycka-WojdalaMichał BieńkowskiRadzisław KordekIzabela ZawlikTermedia Publishing Housearticlemicrornamgmttp53o6-methylguanine-dna methyltransferaseglioblastoma multiforme (gbm)gbMedicineRENArchives of Medical Science, Vol 15, Iss 2, Pp 504-512 (2019)
institution DOAJ
collection DOAJ
language EN
topic microrna
mgmt
tp53
o6-methylguanine-dna methyltransferase
glioblastoma multiforme (gbm)
gb
Medicine
R
spellingShingle microrna
mgmt
tp53
o6-methylguanine-dna methyltransferase
glioblastoma multiforme (gbm)
gb
Medicine
R
Dorota Jesionek-Kupnicka
Marcin Braun
Berenika Trąbska-Kluch
Joanna Czech
Małgorzata Szybka
Bożena Szymańska
Dominika Kulczycka-Wojdala
Michał Bieńkowski
Radzisław Kordek
Izabela Zawlik
MiR-21, miR-34a, miR-125b, miR-181d and miR-648 levels inversely correlate with MGMT and TP53 expression in primary glioblastoma patients
description Introduction TP53 and MGMT alterations play a crucial role in glioblastoma (GB) pathogenesis. TP53 and MGMT function is affected by several pathologic mechanisms, such as point mutations or promoter methylation, which are well characterized. Expression of both genes can be regulated by other mechanisms as well, e.g., microRNAs (miRNAs). Moreover, cross-talk among various pathologic processes may occur, further affecting MGMT and TP53 functionality. Material and methods In 49 GB patients, we analyzed the possible associations between TP53 and its miRNA regulators miR-125b, miR-21, and miR-34a, as well as MGMT and its miRNA regulators miR-181d and miR-648. We evaluated the possible influence of mutational and methylation status on the pre-identified associations. Results In patients with immunohistochemistry-detected TP53 overexpression, expression levels of miR-34a and TP53 were negatively correlated (r = –0.56, p = 0.0195), and in patients with TP53 mutations, expression levels of TP53 and miR-21 were negatively correlated (r = –0.67, p = 0.0330). In patients with MGMT methylation, expression levels of MGMT were negatively correlated with miR-648 and miR-125b expression levels (r = –0.61, p = 0.0269 and r = –0.34, p = 0.0727, respectively). Conclusions Our findings demonstrate that selected miRNAs are significantly correlated with MGMT and TP53 levels, but the extent of this correlation differs regarding the TP53 and MGMT mutational and promoter methylation status.
format article
author Dorota Jesionek-Kupnicka
Marcin Braun
Berenika Trąbska-Kluch
Joanna Czech
Małgorzata Szybka
Bożena Szymańska
Dominika Kulczycka-Wojdala
Michał Bieńkowski
Radzisław Kordek
Izabela Zawlik
author_facet Dorota Jesionek-Kupnicka
Marcin Braun
Berenika Trąbska-Kluch
Joanna Czech
Małgorzata Szybka
Bożena Szymańska
Dominika Kulczycka-Wojdala
Michał Bieńkowski
Radzisław Kordek
Izabela Zawlik
author_sort Dorota Jesionek-Kupnicka
title MiR-21, miR-34a, miR-125b, miR-181d and miR-648 levels inversely correlate with MGMT and TP53 expression in primary glioblastoma patients
title_short MiR-21, miR-34a, miR-125b, miR-181d and miR-648 levels inversely correlate with MGMT and TP53 expression in primary glioblastoma patients
title_full MiR-21, miR-34a, miR-125b, miR-181d and miR-648 levels inversely correlate with MGMT and TP53 expression in primary glioblastoma patients
title_fullStr MiR-21, miR-34a, miR-125b, miR-181d and miR-648 levels inversely correlate with MGMT and TP53 expression in primary glioblastoma patients
title_full_unstemmed MiR-21, miR-34a, miR-125b, miR-181d and miR-648 levels inversely correlate with MGMT and TP53 expression in primary glioblastoma patients
title_sort mir-21, mir-34a, mir-125b, mir-181d and mir-648 levels inversely correlate with mgmt and tp53 expression in primary glioblastoma patients
publisher Termedia Publishing House
publishDate 2019
url https://doaj.org/article/9878f2c77af748089cded2e35d56be05
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