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外泌体长链非编码RNA在肝脏疾病中的动态作用:发病机制与诊断方面

Dynamic role of exosomal long non-coding RNA in liver diseases: pathogenesis and diagnostic aspects.

作者信息

Ismail Mohammed, Fadul Missaa M, Taha Reham, Siddig Orwa, Elhafiz Muhanad, Yousef Bashir A, Jiang Zhenzhou, Zhang Luyong, Sun Lixin

机构信息

Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.

Department of Pharmacology, Faculty of Medicine and Health Science, Dongola University, Dongola, Sudan.

出版信息

Hepatol Int. 2024 Dec;18(6):1715-1730. doi: 10.1007/s12072-024-10722-1. Epub 2024 Sep 21.

Abstract

BACKGROUND

Liver disease has emerged as a significant health concern, characterized by high rates of morbidity and mortality. Circulating exosomes have garnered attention as important mediators of intercellular communication, harboring protein and stable mRNAs, microRNAs, and long non-coding RNAs (lncRNA). This review highlights the involvement of exosomal lncRNA in the pathogenesis and diagnosis of various liver diseases. Notably, exosomal lncRNAs exhibit therapeutic potential as targets for conditions including hepatic carcinoma, hepatic fibrosis, and hepatic viral infections.

METHOD

An online screening process was employed to identify studies investigating the association between exosomal lncRNA and various liver diseases.

RESULT

Our study revealed a diverse array of lncRNAs carried by exosomes, including H19, Linc-ROR, VLDLR, MALAT1, DANCR, HEIH, ENSG00000248932.1, ENST00000457302.2, ZSCAN16-AS1, and others, exhibiting varied levels across different liver diseases compared to normal liver tissue. These exosomal-derived lncRNAs are increasingly recognized as pivotal biomarkers for diagnosing and prognosticating liver diseases, supported by emerging evidence. However, the precise mechanisms underlying the involvement of certain exosomal lncRNAs remain incompletely understood. Furthermore, the combined analysis of serum exosomes using ENSG00000258332.1, LINC00635, and serum AFP may serve as novel and valuable biomarker for HCC. Clinically, exosomal ATB expression is upregulated in HCC, while exosomal HEIH and RP11-513I15.6 have shown potential for distinguishing HCC related to HCV infection.

CONCLUSION

The lack of reliable biomarkers for liver diseases, coupled with the high specificity and sensitivity of exosomal lncRNA and its non-invasive detection, promotes exploring their role in pathogenesis and biomarker for diagnosis, prognosis, and response to treatment liver diseases.

摘要

背景

肝脏疾病已成为一个重大的健康问题,其特点是发病率和死亡率很高。循环外泌体作为细胞间通讯的重要介质而受到关注,其中含有蛋白质、稳定的信使核糖核酸(mRNA)、微小核糖核酸(miRNA)和长链非编码核糖核酸(lncRNA)。本综述重点介绍了外泌体lncRNA在各种肝脏疾病发病机制和诊断中的作用。值得注意的是,外泌体lncRNA作为肝癌、肝纤维化和肝病毒感染等疾病的靶点具有治疗潜力。

方法

采用在线筛选程序来确定研究外泌体lncRNA与各种肝脏疾病之间关联的研究。

结果

我们的研究揭示了外泌体携带的多种lncRNA,包括H19、Linc-ROR、极低密度脂蛋白受体(VLDLR)、转移相关的肺腺癌转录物1(MALAT1)、分化拮抗非蛋白编码RNA(DANCR)、高表达在肝癌中的lncRNA(HEIH)、ENSG00000248932.1、ENST00000457302.2、锌指扫描16反义RNA1(ZSCAN16-AS1)等,与正常肝组织相比,它们在不同肝脏疾病中的水平各不相同。这些外泌体来源的lncRNA越来越被认为是诊断和预测肝脏疾病的关键生物标志物,新出现的证据支持这一点。然而,某些外泌体lncRNA参与其中的确切机制仍未完全了解。此外,使用ENSG00000258332.1、LINC00635和血清甲胎蛋白(AFP)对血清外泌体进行联合分析可能作为肝癌的新型有价值生物标志物。临床上,外泌体激活素A结合蛋白(ATB)在肝癌中表达上调,而外泌体HEIH和RP11-513I15.6已显示出区分丙型肝炎病毒(HCV)感染相关肝癌的潜力。

结论

肝脏疾病缺乏可靠的生物标志物,加上外泌体lncRNA的高特异性和敏感性及其非侵入性检测,促使人们探索它们在发病机制中的作用以及作为肝脏疾病诊断、预后和治疗反应的生物标志物。

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