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长链非编码 RNA 在胸主动脉瘤和腹主动脉瘤发展中的发病机制意义。

Pathogenetic Significance of Long Non-Coding RNAs in the Development of Thoracic and Abdominal Aortic Aneurysms.

机构信息

Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634050, Russia.

出版信息

Biochemistry (Mosc). 2024 Jan;89(1):130-147. doi: 10.1134/S0006297924010085.

Abstract

Aortic aneurysm (AA) is a life-threatening condition with a high prevalence and risk of severe complications. The aim of this review was to summarize the data on the role of long non-coding RNAs (lncRNAs) in the development of AAs of various location. Within less than a decade of studies on the role of lncRNAs in AA, using experimental and bioinformatic approaches, scientists have obtained the data confirming the involvement of these molecules in metabolic pathways and pathogenetic mechanisms critical for the aneurysm development. Regardless of the location of pathological process (thoracic or abdominal aorta), AA was found to be associated with changes in the expression of various lncRNAs in the tissue of the affected vessels. The consistency of changes in the expression level of lncRNA, mRNA and microRNA in aortic tissues during AA development has been recordedand regulatory networks implicated in the AA pathogenesis in which lncRNAs act as competing endogenous RNAs (ceRNA networks) have been identified. It was found that the same lncRNA can be involved in different ceRNA networks and regulate different biochemical and cellular events; on the other hand, the same pathological process can be controlled by different lncRNAs. Despite some similarities in pathogenesis and overlapping of involved lncRNAs, the ceRNA networks described for abdominal and thoracic AA are different. Interactions between lncRNAs and other molecules, including those participating in epigenetic processes, have also been identified as potentially relevant to the AA pathogenesis. The expression levels of some lncRNAs were found to correlate with clinically significant aortic features and biochemical parameters. Identification of regulatory RNAs functionally significant in the aneurysm development is important for clarification of disease pathogenesis and will provide a basis for early diagnostics and development of new preventive and therapeutic drugs.

摘要

主动脉瘤(AA)是一种危及生命的疾病,其发病率和严重并发症的风险都很高。本综述的目的是总结长链非编码 RNA(lncRNA)在各种部位的 AA 发展中的作用的数据。在对 lncRNA 在 AA 中的作用进行研究的不到十年时间里,科学家们通过实验和生物信息学方法获得了数据,证实了这些分子参与了对动脉瘤发展至关重要的代谢途径和发病机制。无论病变部位(胸主动脉或腹主动脉)如何,AA 都与受影响血管组织中各种 lncRNA 的表达变化有关。在 AA 发展过程中,lncRNA、mRNA 和 microRNA 在主动脉组织中的表达水平变化的一致性已经被记录下来,并且已经确定了涉及 lncRNA 作为竞争内源性 RNA(ceRNA 网络)的 AA 发病机制的调节网络。研究发现,同一 lncRNA 可以参与不同的 ceRNA 网络,并调节不同的生化和细胞事件;另一方面,不同的 lncRNA 可以控制相同的病理过程。尽管发病机制存在一些相似性,涉及的 lncRNA 有重叠,但描述的腹主动脉瘤和胸主动脉瘤的 ceRNA 网络是不同的。lncRNA 与其他分子(包括参与表观遗传过程的分子)之间的相互作用也被认为与 AA 的发病机制有关。一些 lncRNA 的表达水平与临床意义重大的主动脉特征和生化参数相关。鉴定在动脉瘤发展中具有功能意义的调节 RNA 对于阐明疾病的发病机制非常重要,并且将为早期诊断和开发新的预防和治疗药物提供基础。

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