Methylation-associated Silencing of microRNA-126 and its Host Gene EGFL7 in Malignant Pleural Mesothelioma
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BACKGROUND/AIM: We recently reported that miR-126 is down-regulated in malignant pleural mesothelioma (MPM) and can be combined into a 4-microRNA-classifier that can accurately diagnose MPM with high sensitivity and specificity. Herein we analyzed the epigenetic regulation of miR-126 and its host gene EGF-like domain, multiple 7 (EGFL7).
MATERIALS AND METHODS: Resected formalin-fixed paraffin-embedded MPM tissues from 29 patients, 14 patient-matched non-neoplastic pleura (NNP) specimens, 5 MPM diagnostic biopsies (DB), and 5 samples of pneumothorax-induced benign reactive mesothelial proliferation (PTHX) were analyzed. miR-126 and EGFL7 mRNA were quantified by RT-qPCR. CpG-islands' methylation in the EGFL7 promoter was analyzed using methylation-specific PCR and in the MIR126-containing intron 7 was quantified by pyrosequencing.
RESULTS: Relative to NNP, EGFL7 was under-expressed more than 4-fold in MPM (p<0.001). EGFL7 mRNA and miR-126 levels correlated in MPM (p<0.01) and NNP (p<0.001). The EGFL7 promoter region was hypermethylated in 69% of MPM and 80% of DB samples, but not in NNP and PTHX samples. EGFL7 promoter hypermethylation was associated with epithelioid histology (p<0.05) and reduced patient-survival (p<0.05).
CONCLUSION: In MPM, DNA-hypermethylation down-regulates miR-126 and its host gene EGFL7, therefore is a poor prognostic factor, and may represent a future therapeutic target for de-methylating strategies re-establishing EGFL7 and miR-126 expression.
Original language | English |
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Journal | Anticancer Research |
Volume | 35 |
Issue number | 11 |
Pages (from-to) | 6223-9 |
Number of pages | 7 |
ISSN | 0250-7005 |
Publication status | Published - Nov 2015 |
- Adult, Aged, Biomarkers, Tumor, Case-Control Studies, DNA Methylation, Endothelial Growth Factors, Epigenesis, Genetic, Female, Follow-Up Studies, Gene Expression Regulation, Neoplastic, Humans, Lung Neoplasms, Male, Mesothelioma, MicroRNAs, Middle Aged, Neoplasm Staging, Pleural Neoplasms, Prognosis, Promoter Regions, Genetic, Real-Time Polymerase Chain Reaction
Research areas
Links
- http://ar.iiarjournals.org.ep.fjernadgang.kb.dk/content/35/11/6223
Final published version
ID: 161271010