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环状 RNA 的表达和相互作用模式在肌萎缩侧索硬化症中受到干扰。

Circular RNA Expression and Interaction Patterns Are Perturbed in Amyotrophic Lateral Sclerosis.

机构信息

GenieUs Genomics Pty Ltd., Sydney, NSW 2010, Australia.

School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.

出版信息

Int J Mol Sci. 2022 Nov 24;23(23):14665. doi: 10.3390/ijms232314665.

Abstract

Circular RNAs (circRNAs) are a type of long noncoding RNA that are highly abundant and highly conserved throughout evolution and exhibit differential expression patterns in various tissue types in multiple diseases, including amyotrophic lateral sclerosis (ALS). The most well-known function of circRNAs is their ability to act as microRNA (miRNA) sponges. This entails circRNA binding to miRNA, which would otherwise target and degrade messenger RNA, thus affecting gene expression. This study analyzed ALS patient samples from three spinal cord regions to investigate circular transcriptome perturbation and circular RNA-microRNA-mRNA interactions. Using stringent statistical parameters, we identified 92 differentially expressed circRNAs across the spinal cord tissues with the aim of identifying specific circRNAs with biomarker potential. We also found evidence for differential expression of 37 linear RNAs possibly due to miRNA sequestration by circRNAs, thus revealing their potential as novel biomarkers and therapeutic candidates for ALS.

摘要

环状 RNA(circRNAs)是一种长非编码 RNA,在进化过程中高度丰富且高度保守,并在多种疾病的不同组织类型中表现出不同的表达模式,包括肌萎缩侧索硬化症(ALS)。circRNAs 最著名的功能是其作为 microRNA(miRNA)海绵的能力。这需要 circRNA 与 miRNA 结合,否则 miRNA 会靶向并降解信使 RNA,从而影响基因表达。本研究分析了来自三个脊髓区域的 ALS 患者样本,以研究环状转录组的扰动和环状 RNA-miRNA-mRNA 相互作用。使用严格的统计参数,我们在整个脊髓组织中鉴定出 92 个差异表达的 circRNAs,旨在鉴定具有潜在生物标志物的特定 circRNAs。我们还发现了 37 个线性 RNA 差异表达的证据,可能是由于 circRNAs 对 miRNA 的隔离,从而揭示了它们作为 ALS 新型生物标志物和治疗候选物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338a/9739162/1f81a5fe9023/ijms-23-14665-g001.jpg

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