多发性硬化症中可变剪接变体的异常表达 - 系统评价。

Aberrant expression of alternative splicing variants in multiple sclerosis - A systematic review.

机构信息

University of Rostock, Department of Neurology, Division of Neuroimmunology, Gehlsheimer Str. 20, 18147 Rostock, Germany.

出版信息

Autoimmun Rev. 2019 Jul;18(7):721-732. doi: 10.1016/j.autrev.2019.05.010. Epub 2019 May 4.

DOI:10.1016/j.autrev.2019.05.010

PMID:31059848

Abstract

OBJECTIVE

Alternative splicing is an important form of RNA processing that affects nearly all human genes. The differential expression of specific transcript and protein isoforms holds the potential of novel biomarkers for complex diseases. In this systematic review, we compiled the existing literature on aberrant alternative splicing events in multiple sclerosis (MS).

METHODS

A systematic literature search in the PubMed database was carried out and supplemented by screening the reference lists of the identified articles. We selected only MS-related original research studies which compared the levels of different isoforms of human protein-coding genes. A narrative synthesis of the research findings was conducted. Additionally, we performed a case-control analysis using high-density transcriptome microarray data to reevaluate the genes that were examined in the reviewed studies.

RESULTS

A total of 160 records were screened. Of those, 36 studies from the last two decades were included. Most commonly, peripheral blood samples were analyzed (32 studies), and PCR-based techniques were usually employed (27 studies) for measuring the expression of selected genes. Two studies used an exploratory genome-wide approach. Overall, 27 alternatively spliced genes were investigated. Nine of these genes appeared in at least two studies (CD40, CFLAR, FOXP3, IFNAR2, IL7R, MOG, PTPRC, SP140 and TNFRSF1A). The microarray data analysis confirmed differential alternative pre-mRNA splicing for 19 genes.

CONCLUSIONS

An altered RNA processing of genes mediating immune signaling pathways has been repeatedly implicated in MS. The analysis of individual exon-level expression patterns is stimulated by the advancement of transcriptome profiling technologies. In particular, the examination of genes encoded in MS-associated genetic regions may provide important insights into the pathogenesis of the disease and help to identify new biomarkers.

摘要

目的

可变剪接是一种重要的 RNA 加工形式，几乎影响所有人类基因。特定转录本和蛋白质亚型的差异表达可能成为复杂疾病的新型生物标志物。在本系统综述中，我们整理了多发性硬化症（MS）中异常可变剪接事件的现有文献。

方法

我们在 PubMed 数据库中进行了系统的文献检索，并通过筛选已确定文章的参考文献进行了补充。我们仅选择了比较人类蛋白编码基因不同亚型水平的与 MS 相关的原始研究。对研究结果进行了叙述性综合分析。此外，我们使用高密度转录组微阵列数据进行了病例对照分析，以重新评估在综述研究中检查的基因。

结果

共筛选出 160 条记录，其中包括过去 20 年的 36 项研究。最常见的是分析外周血样本（32 项研究），并且通常采用基于 PCR 的技术（27 项研究）来测量所选基因的表达。两项研究采用了探索性的全基因组方法。总体而言，研究了 27 个可变剪接基因。其中 9 个基因出现在至少两项研究中（CD40、CFLAR、FOXP3、IFNAR2、IL7R、MOG、PTPRC、SP140 和 TNFRSF1A）。微阵列数据分析证实了 19 个基因的差异选择性前 mRNA 剪接。