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Cell-free microRNAs in Parkinson's disease: potential biomarkers that provide new insights into disease pathogenesis.
Ageing Research Reviews ( IF 13.1 ) Pub Date : 2020-01-27 , DOI: 10.1016/j.arr.2020.101023
Epaminondas Doxakis 1
Affiliation  

MicroRNAs (miRNAs) are master post-transcriptional regulators of gene expression and their specific footprints reflect disease conditions. Over the last few years, several primary reports have described the deregulation of cell-free miRNAs in Parkinson’s disease (PD), however, results have been rather inconsistent due to preanalytical and analytical challenges. This study integrated the data across twenty-four reports to identify steadily deregulated miRNAs that may assist in the path towards biomarker development and molecular characterization of the underlying pathology. Stringent KEGG pathway analysis of the miRNA targets revealed FoxO, Prolactin, TNF, and ErbB signaling pathways as the most significantly enriched categories while Gene Ontology analysis revealed that the protein targets are mostly associated with transcription. Chromosomal location of the consistently deregulated miRNAs revealed that over a third of them were clustered at the same location at Chr14q32 suggesting that they are co-regulated by specific transcription factors. This genomic region is inherently unstable due to expanded TGG repeats and responsible for human abnormalities. Stringent analysis of transcription factor sites surrounding the deregulated miRNAs revealed that CREB1, CEBPB and MAZ sites existed in approximately half of the miRNAs, including all of the miRNAs located at Chr14q32. Additional studies are now needed to determine the biomarker potential of the consistently deregulated miRNAs in PD and the therapeutic implications of these bioinformatics insights.



中文翻译:

帕金森氏病中的无细胞microRNA:潜在的生物标志物,可为疾病发病机理提供新的见解。

微小RNA(miRNA)是基因表达的主要转录后调节因子,其特定足迹可反映疾病状况。在过去的几年中,一些主要的报告描述了帕金森氏病(PD)中无细胞miRNA的失控,但是由于分析和分析方面的挑战,结果一直不一致。这项研究整合了24份报告中的数据,以鉴定稳定释放的miRNA,这些miRNA可能有助于生物标志物发展和潜在病理学的分子表征。对miRNA靶标进行严格的KEGG通路分析后发现,FoxO,催乳素,TNF和ErbB信号通路是最显着富集的类别,而基因本体分析表明,蛋白质靶标大多与转录相关。始终被失调的miRNA的染色体位置显示,超过三分之一的miRNA聚集在Chr14q32的相同位置,表明它们受特定转录因子的共同调控。由于扩展的TGG重复序列,该基因组区域固有地不稳定,并导致人类异常。围绕失调的miRNA的转录因子位点的严格分析显示,CREB1,CEBPB和MAZ位点存在于大约一半的miRNA中,包括位于Chr14q32的所有miRNA。现在需要进行进一步的研究,以确定PD中持续释放的miRNA的生物标志物潜力以及这些生物信息学见解的治疗意义。

更新日期:2020-01-27
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