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      Roles of long noncoding RNAs in human inflammatory diseases

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          Abstract

          Chemokines, cytokines, and inflammatory cells mediate the onset and progression of many diseases through the induction of an inflammatory response. LncRNAs have emerged as important regulators of gene expression and signaling pathways. Increasing evidence suggests that lncRNAs are key players in the inflammatory response, making it a potential therapeutic target for various diseases. From the perspective of lncRNAs and inflammatory factors, we summarized the expression level and regulatory mechanisms of lncRNAs in human inflammatory diseases, such as cardiovascular disease, osteoarthritis, sepsis, chronic obstructive pulmonary disease, asthma, acute lung injury, diabetic retinopathy, and Parkinson’s disease. We also summarized the functions of lncRNAs in the macrophages polarization and discussed the potential applications of lncRNAs in human inflammatory diseases. Although our understanding of lncRNAs is still in its infancy, these data will provide a theoretical basis for the clinical application of lncRNAs.

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          Most cited references102

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          Origin and physiological roles of inflammation.

          Inflammation underlies a wide variety of physiological and pathological processes. Although the pathological aspects of many types of inflammation are well appreciated, their physiological functions are mostly unknown. The classic instigators of inflammation - infection and tissue injury - are at one end of a large range of adverse conditions that induce inflammation, and they trigger the recruitment of leukocytes and plasma proteins to the affected tissue site. Tissue stress or malfunction similarly induces an adaptive response, which is referred to here as para-inflammation. This response relies mainly on tissue-resident macrophages and is intermediate between the basal homeostatic state and a classic inflammatory response. Para-inflammation is probably responsible for the chronic inflammatory conditions that are associated with modern human diseases.
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            Gene regulation by long non-coding RNAs and its biological functions

            Evidence accumulated over the past decade shows that long non-coding RNAs (lncRNAs) are widely expressed and have key roles in gene regulation. Recent studies have begun to unravel how the biogenesis of lncRNAs is distinct from that of mRNAs and is linked with their specific subcellular localizations and functions. Depending on their localization and their specific interactions with DNA, RNA and proteins, lncRNAs can modulate chromatin function, regulate the assembly and function of membraneless nuclear bodies, alter the stability and translation of cytoplasmic mRNAs and interfere with signalling pathways. Many of these functions ultimately affect gene expression in diverse biological and physiopathological contexts, such as in neuronal disorders, immune responses and cancer. Tissue-specific and condition-specific expression patterns suggest that lncRNAs are potential biomarkers and provide a rationale to target them clinically. In this Review, we discuss the mechanisms of lncRNA biogenesis, localization and functions in transcriptional, post-transcriptional and other modes of gene regulation, and their potential therapeutic applications.
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              Functional Classification and Experimental Dissection of Long Noncoding RNAs

              Over the last decade, it has been increasingly demonstrated that the genomes of many species are pervasively transcribed, resulting in the production of numerous long noncoding RNAs (lncRNAs). At the same time, it is now appreciated that many types of DNA regulatory elements, such as enhancers and promoters, regularly initiate bidirectional transcription. Thus, discerning functional noncoding transcripts from a vast transcriptome is a paramount priority, and challenge, for the lncRNA field. In this review, we aim to provide a conceptual and experimental framework for classifying and elucidating lncRNA function. We categorize lncRNA loci into those that regulate gene expression in cis versus those that perform functions in trans , and propose an experimental approach to dissect lncRNA activity based on these classifications. These strategies to further understand lncRNAs promise to reveal new and unanticipated biology, with great potential to advance our understanding of normal physiology and disease.
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                Author and article information

                Contributors
                zhangyl@sxent.org
                zcmsxmu@sxent.org
                Journal
                Cell Death Discov
                Cell Death Discov
                Cell Death Discovery
                Nature Publishing Group UK (London )
                2058-7716
                15 May 2024
                15 May 2024
                2024
                : 10
                : 235
                Affiliations
                [1 ]Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, ( https://ror.org/02vzqaq35) Taiyuan, 030001 Shanxi China
                [2 ]Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, ( https://ror.org/02vzqaq35) Taiyuan, 030001 Shanxi China
                [3 ]Department of Otolaryngology Head & Neck Surgery, First Hospital of Shanxi Medical University, ( https://ror.org/02vzqaq35) Taiyuan, Shanxi 030001 China
                Author information
                http://orcid.org/0000-0002-0871-1363
                Article
                2002
                10.1038/s41420-024-02002-6
                11096177
                38750059
                9f9f0e22-d941-432f-b2c6-dacc4b921bdb
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 6 July 2023
                : 30 April 2024
                : 2 May 2024
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100004480, Natural Science Foundation of Shanxi Province (Shanxi Province Natural Science Foundation);
                Award ID: 2021030224704
                Award ID: 202203021212034
                Award ID: 202203021212045
                Award Recipient :
                Funded by: Innovation team of medical science and technology in Shanxi (China) (no, 2020TD26).
                Categories
                Review Article
                Custom metadata
                © Cell Death Differentiation Association (ADMC) 2024

                mechanisms of disease,long non-coding rnas
                mechanisms of disease, long non-coding rnas

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