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

Dorota Jesionek-Kupnicka; Marcin Braun; Berenika Trąbska-Kluch; Joanna Czech; Małgorzata Szybka; Bożena Szymańska; Dominika Kulczycka-Wojdala; Michał Bieńkowski; Radzisław Kordek; Izabela Zawlik

doi:10.5114/aoms.2017.69374

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

Arch Med Sci. 2019 Mar;15(2):504-512. doi: 10.5114/aoms.2017.69374. Epub 2017 Jul 31.

Authors

Affiliations

¹ Department of Pathology, Chair of Oncology, Medical University of Lodz, Lodz, Poland.
² Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland.
³ Department of Radiotherapy, Medical University of Lodz, Lodz, Poland.
⁴ Department of Genetics, Chair of Molecular Medicine, Faculty of Medicine, University of Rzeszow, Rzeszow, Poland.
⁵ Laboratory of Molecular Biology, Centre for Innovative Research in Medical and Natural Sciences, University of Rzeszow, Rzeszow, Poland.
⁶ Department of Microbiology and Laboratory Medical Immunology, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
⁷ Central Scientific Laboratory, Medical University of Lodz, Lodz, Poland.
⁸ Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland.

Abstract

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.

Keywords: GB; MGMT; O6-methylguanine-DNA methyltransferase; TP53; microRNA.