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调控调控因子:长链非编码RNA作为慢性疾病管理中的自噬调控因子

Regulating the regulators: long non-coding RNAs as autophagic controllers in chronic disease management.

作者信息

Kumar Aviral, Yap Kenneth Chun-Hong, BharathwajChetty Bandari, Lyu Juncheng, Hegde Mangala, Abbas Mohamed, Alqahtani Mohammed S, Khadlikar Soham, Zarrabi Ali, Khosravi Arezoo, Kumar Alan Prem, Kunnumakkara Ajaikumar B

机构信息

Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam, 781039, India.

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.

出版信息

J Biomed Sci. 2024 Dec 23;31(1):105. doi: 10.1186/s12929-024-01092-9.

Abstract

The increasing prevalence of chronic diseases and their associated morbidities demands a deeper understanding of underlying mechanism and causative factors, with the hope of developing novel therapeutic strategies. Autophagy, a conserved biological process, involves the degradation of damaged organelles or protein aggregates to maintain cellular homeostasis. Disruption of this crucial process leads to increased genomic instability, accumulation of reactive oxygen species (ROS), decreased mitochondrial functions, and suppression of ubiquitination, leading to overall decline in quality of intracellular components. Such deregulation has been implicated in a wide range of pathological conditions such as cancer, cardiovascular, inflammatory, and neurological disorders. This review explores the role of long non-coding RNAs (lncRNAs) as modulators of transcriptional and post-transcriptional gene expression, regulating diverse physiological process like proliferation, development, immunity, and metabolism. Moreover, lncRNAs are known to sequester autophagy related microRNAs by functioning as competing endogenous RNAs (ceRNAs), thereby regulating this vital process. In the present review, we delineate the multitiered regulation of lncRNAs in the autophagic dysfunction of various pathological diseases. Moreover, by highlighting recent findings on the modulation of lncRNAs in different stages of autophagy, and the emerging clinical landscape that recognizes lncRNAs in disease diagnosis and therapy, this review highlights the potential of lncRNAs as biomarkers and therapeutic targets in clinical settings of different stages of autophagic process by regulating ATG and its target genes. This focus on lncRNAs could lead to breakthroughs in personalized medicine, offering new avenues for diagnosis and treatment of complex diseases.

摘要

慢性病及其相关发病率的日益普遍,要求我们更深入地了解其潜在机制和致病因素,以期开发新的治疗策略。自噬是一个保守的生物学过程,涉及受损细胞器或蛋白质聚集体的降解,以维持细胞内稳态。这一关键过程的破坏会导致基因组不稳定性增加、活性氧(ROS)积累、线粒体功能下降以及泛素化抑制,从而导致细胞内成分质量整体下降。这种失调与多种病理状况有关,如癌症、心血管疾病、炎症和神经疾病。本综述探讨了长链非编码RNA(lncRNA)作为转录和转录后基因表达调节剂的作用,其调节增殖、发育、免疫和代谢等多种生理过程。此外,已知lncRNA通过作为竞争性内源RNA(ceRNA)来隔离自噬相关的微小RNA,从而调节这一重要过程。在本综述中,我们阐述了lncRNA在各种病理疾病自噬功能障碍中的多层次调节。此外,通过强调lncRNA在自噬不同阶段调节的最新发现,以及在疾病诊断和治疗中认识到lncRNA的新兴临床前景,本综述强调了lncRNA通过调节自噬相关基因(ATG)及其靶基因,在自噬过程不同阶段的临床环境中作为生物标志物和治疗靶点的潜力。对lncRNA的关注可能会带来个性化医学的突破,为复杂疾病的诊断和治疗提供新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3757/11667983/280d73d472cd/12929_2024_1092_Fig1_HTML.jpg

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