Analysis of EZH2: micro-RNA network in low and high grade astrocytic tumors
Autor: | Shashank S. Kale, Vikas Sharma, Anupam Kumar, Ritu Kulshreshtha, Suvendu Purkait, Pankaj Pathak, Ashish Suri, Mehar Chand Sharma, Sonam Takkar, Prit Benny Malgulwar, Chitra Sarkar, Vaishali Suri |
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Rok vydání: | 2016 |
Předmět: |
Adult
Male 0301 basic medicine Cancer Research Gene Expression macromolecular substances Astrocytoma Biology Young Adult 03 medical and health sciences Downregulation and upregulation microRNA Gene expression Humans Enhancer of Zeste Homolog 2 Protein Molecular Targeted Therapy Enhancer Gene Aged Neoplasm Staging Oncogene Brain Neoplasms EZH2 RNA Epistasis Genetic General Medicine Middle Aged MicroRNAs 030104 developmental biology Oncology Disease Progression Cancer research Female Neurology (clinical) Glioblastoma |
Zdroj: | Brain Tumor Pathology. 33:117-128 |
ISSN: | 1861-387X 1433-7398 |
Popis: | 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. |
Databáze: | OpenAIRE |
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