Fazeli Zahra, Ghaderian Sayyed Mohammad Hossein, Najmabadi Hossein, Omrani Mir Davood
Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Cell Biochem. 2019 Feb;120(2):1916-1923. doi: 10.1002/jcb.27505. Epub 2018 Aug 30.
MicroRNAs (miRNAs) have been found to play an important role in the regulation of gene expression in eukaryotic organisms at the posttranscriptional level. More than half of miRNA genes have been recognized to be located in different fragile sites. Among them, miR-510 was located on chromosome X in the 27.3Xq region, flanking to a fragile X site. The CGG expansion and its methylation at the promoter of FMR1 located in this fragile site were associated with clinical symptoms of fragile X syndrome (FXS). The aim of the current study was to investigate whether the miR-510 expression was correlated with the CGG expansion of FMR1 in female carriers of full mutation. For this purpose, mesenchymal stem cells were isolated from peripheral blood of FMR1 full mutation female carriers. After differentiation of these cells into neuronal cells, the expression of miR-510 was analyzed by quantitative polymerase chain reaction. Furthermore, the target genes of miR-510 in the nervous system were also predicted by in silico method. The obtained results indicated that the CGG expansion of FMR1 was associated with the enhanced expression of miR-510. Furthermore, the bioinformatics analysis suggested that VHL and PPP2R5E genes could be considered as the most important target genes of miR-510 in the nervous system. This study showed that miR-510 and its target genes, specifically VHL and PPP2R5E, may represent the new targets for future therapy options of FXS.
微小RNA（miRNA）已被发现在真核生物基因表达的转录后水平调控中发挥重要作用。超过半数的miRNA基因被认为位于不同的脆性位点。其中，miR-510位于X染色体的27.3Xq区域，毗邻一个脆性X位点。位于该脆性位点的FMR1启动子处的CGG重复序列扩增及其甲基化与脆性X综合征（FXS）的临床症状相关。本研究的目的是调查miR-510的表达是否与完全突变女性携带者中FMR1的CGG重复序列扩增相关。为此，从FMR1完全突变女性携带者的外周血中分离间充质干细胞。将这些细胞分化为神经细胞后，通过定量聚合酶链反应分析miR-510的表达。此外，还通过计算机模拟方法预测了miR-510在神经系统中的靶基因。所得结果表明，FMR1的CGG重复序列扩增与miR-510的表达增强相关。此外，生物信息学分析表明，VHL和PPP2R5E基因可能是miR-510在神经系统中最重要的靶基因。本研究表明，miR-510及其靶基因，特别是VHL和PPP2R5E，可能代表FXS未来治疗选择的新靶点。
