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01-04-2016 | Original Article

Analysis of EZH2: micro-RNA network in low and high grade astrocytic tumors

Authors: Vikas Sharma, Suvendu Purkait, Sonam Takkar, Prit Benny Malgulwar, Anupam Kumar, Pankaj Pathak, Vaishali Suri, Mehar C. Sharma, Ashish Suri, Shashank Sharad Kale, Ritu Kulshreshtha, Chitra Sarkar

Published in: Brain Tumor Pathology | Issue 2/2016

Abstract

Enhancer of Zeste homologue2 (EZH2) is an epigenetic regulator that functions as oncogene in astrocytic tumors, however, EZH2 regulation remains little studied. In this study, we measured EZH2 levels in low (Gr-II,DA) and high grade (Gr-IV,GBM) astrocytic tumors and found significant increased EZH2 transcript level with grade(median DA-8.5, GBM-28.9).However, a different trend was reflected in protein levels, with GBMs showing high EZH2 LI(median-26.5) compared to DA (median 0.3). This difference in correlation of EZH2 protein and RNA levels suggested post-transcriptional regulation of EZH2, likely mediated by miRNAs. We selected eleven miRNAs that strongly predicted to target EZH2 and measured their expression. Three miRNAs (miR-26a-5p,miR27a-3p and miR-498) showed significant correlation with EZH2 protein, suggesting them as regulators of EZH2, however miR-26a-5p levels decreased with grade. ChIP analyses revealed H3K27me3 modifications in miR-26a promoter suggesting feedback loop between EZH2 and miR26a. We further measured six downstream miRNA targets of EZH2 and found significant downregulation of four (miR-181a/b and 200b/c) in GBM. Interestingly, EZH2 associated miRNAs were predicted to target 25 genes in glioma-pathway, suggesting their role in tumor formation or progression. Collectively, our work suggests EZH2 and its miRNA interactors may serve as promising biomarkers for progression of astrocytic tumors and may offer novel therapeutic strategies.

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Title: Analysis of EZH2: micro-RNA network in low and high grade astrocytic tumors
Authors: Vikas Sharma
Suvendu Purkait
Sonam Takkar
Prit Benny Malgulwar
Anupam Kumar
Pankaj Pathak
Vaishali Suri
Mehar C. Sharma
Ashish Suri
Shashank Sharad Kale
Ritu Kulshreshtha
Chitra Sarkar
Publication date: 01-04-2016
Publisher: Springer Japan
Published in: Brain Tumor Pathology / Issue 2/2016
Print ISSN: 1433-7398
Electronic ISSN: 1861-387X
DOI: https://doi.org/10.1007/s10014-015-0245-1

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Analysis of EZH2: micro-RNA network in low and high grade astrocytic tumors

Abstract

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