High expression of miR‐510 was associated with CGG expansion located at upstream of FMR1 into full mutation

Abstract

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.

Non-coding RNA in Fragile X Syndrome and Converging Mechanisms Shared by Related Disorders

“…In the brain, miR-510, located near the fragile site on X chromosome, was associated with CGG expansion into full mutation in the neurons derived from mesenchymal stem cells. Bioinformatics analysis indicated that enhanced miR-510 expression might facilitate CGG expansion via regulating target genes such as VHL and PPP2R5E (Fazeli et al, 2018). In mice embryonic NPC, the upregulation of miR-130b associates with decreased FMRP level and increased NPC proliferation tendency (Gong et al, 2013).…”

Identification of microRNAs associated with human fragile X syndrome using next-generation sequencing

“…Subsequent studies in the FMR1 KO mouse models found that disruption of the regulating of miR-125a, miR-125b, and miR-132 causes early neural development and synaptic physiology 18 and that there is an interaction between miR-34b, miR-340, and miR-148a with the Met 3′ UTR of the FMR1 gene 39 . Moreover, by isolating mesenchymal stem cells from peripheral blood and differentiating these cells into neuronal cells, Fazeli et al 40 recently analyzed the expression of miR-510 by the qPCR method. The authors reported an enhanced expression of miR-510, located on chromosome X in the 27.3Xq region, flanking to a fragile X site, in the female carriers of FMR1 full mutation.…”

Identification of microRNAs Associated With Human Fragile X Syndrome Using Next Generation Sequencing

“…Subsequent studies in the Fmr1 KO mouse models found that disruption of the regulating of miR-125a, miR-125b, and miR-132 causes early neural development and synaptic physiology [30] and that there is an interaction between miR-34b, miR-340, and miR-148a with the Met 3′ UTR of the FMR1 gene [31]. Moreover, by isolating mesenchymal stem cells from peripheral blood and differentiating these cells into neuronal cells, Fazeli et al [32] recently analyzed the expression of miR-510 by qPCR method. The authors reported an enhanced expression of miR-510, located on chromosome X in the 27.3Xq region, anking to a fragile X site, in the female carriers of FMR1 full mutation [32].…”

“…Moreover, by isolating mesenchymal stem cells from peripheral blood and differentiating these cells into neuronal cells, Fazeli et al [32] recently analyzed the expression of miR-510 by qPCR method. The authors reported an enhanced expression of miR-510, located on chromosome X in the 27.3Xq region, anking to a fragile X site, in the female carriers of FMR1 full mutation [32].…”