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Epigenetic Modification of MicroRNA-205 and its Association with Glioblastoma Multiform by Asghar Ghasemi, Soudabeh Fallah

Background: Deregulated expressions of tumor-suppressive microRNAs (miRNAs) by epigenetic aberrations has a critical role in tumorigenesis. The aim of the present study was to investigate the epigenetic aberrations of miR205 and to understand how this modification may contribute to molecular events in glioblastoma multiform (GBM).
Methods: Quantitative RT-PCR and bisulfite genomic sequencing techniques were used to investigate gene expression and methylation levels of miR-205 in GBM tissues (n = 23), their matched adjacent normal tissues (n = 23) and glioblastoma U87MG cell line. Following treatment of cells with 5-aza-2'-deoxycitidine (5-aza-dC), DNA methylation and gene expression levels of miR-205 gene and protein expressions of its target mRNA were investigated.
Results: Our study showed that gene expression level of miR-205 decreased in GBM tissues compared to controls (p < 0.01) and lower expression was significantly correlated with this miRNA promoter hypermethylation (r = -78; p < 0.01). Cell treatment with 5-aza-dC restored the hypermethylated promoter and gene expression of the miR205 and decreased target mRNA and proteins levels (p < 0.01).
Conclusions: In summary, our results offered that miR-205 is an epigenetically silenced tumor suppressive miRNA in GBM, suppresses enhanced target mRNA when induced by DNA demethylating agents.

DOI: 10.7754/Clin.Lab.2017.161123