Ghasemi Asghar, Fallah Soudabeh
Clin Lab. 2017 Jul 1;63(7):1079-1088. doi: 10.7754/Clin.Lab.2017.161123.
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).
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.
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).
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.
表观遗传异常导致肿瘤抑制性微小RNA（miRNA）表达失调在肿瘤发生中起关键作用。本研究旨在探讨miR205的表观遗传异常，并了解这种修饰如何促进多形性胶质母细胞瘤（GBM）中的分子事件。
采用定量逆转录聚合酶链反应（RT-PCR）和亚硫酸氢盐基因组测序技术，研究miR-205在GBM组织（n = 23）、其配对的相邻正常组织（n = 23）和胶质母细胞瘤U87MG细胞系中的基因表达和甲基化水平。用5-氮杂-2'-脱氧胞苷（5-aza-dC）处理细胞后，研究miR-205基因的DNA甲基化和基因表达水平及其靶mRNA的蛋白质表达。
我们的研究表明，与对照组相比，GBM组织中miR-205的基因表达水平降低（p < 0.01），且较低的表达与该miRNA启动子高甲基化显著相关（r = -78；p < 0.01）。用5-aza-dC处理细胞可恢复miR205高甲基化的启动子和基因表达，并降低靶mRNA和蛋白质水平（p < 0.01）。
总之，我们的结果表明，miR-205是GBM中一种表观遗传沉默的肿瘤抑制性miRNA，在DNA去甲基化剂诱导下可抑制增强的靶mRNA。
