ReviewFunctional crosstalk between Long non-coding RNAs and the NLRP3 inflammasome in the regulation of diseases
Introduction
Inflammation underlies numerous pathological processes involving the action of various inflammatory cells and inflammatory activating factors and serves as the body's initial adaptive response to external stimuli, stress, tumours, metabolic diseases, and allergies(Medzhitov, 2008, 2010). Long noncoding RNAs (lncRNAs) do not encode any proteins longer than 200 nucleotides and were previously regarded as non-functional molecular noise RNA(Gutschner and Diederichs, 2012; Mendell et al., 2004). However, certain annotated lncRNAs that bind to ribosomes and contain a translation region that can translate peptides have gradually been discovered(Nam et al., 2016). LncRNAs regulate related genes by directly or indirectly binding to specific DNA/RNA or protein sites in the cytoplasm or nucleus(Moura et al., 2014). In contrast to miRNAs and circRNAs, lncRNAs have well-conserved sequences and structures and cannot participate in various regulatory mechanisms(Kornfeld and Brüning, 2014). In different biological environments, they perform particular functions and regulate complex natural mechanism; e.g., acting (i) as scaffolds to polymerize protein complexs, (ii) as molecular sponges for ceRNA protagonists, (iii) as host genes of various RNAs (iv) to guide the mRNA degradation process, and isolate of transcription factors for DNA regulation and epigenetic regulation of chromatin conformation, and (v) as protectors of mRNA through the prevention of degradation by binding miRNA(Hadjicharalambous and Lindsay, 2019; Kornfeld and Brüning, 2014; Morlando and Fatica, 2018). Larg high-quality sequencing platform data sets have indicated that the emergence of many inflammatory genes and the activation of signalling pathways found abnormal lncRNA expression (Liao et al., 2018). Pyridine-containing domain 3 (NLRP3), also called the inflammasome, is a multimolecular protein complex that performs a specific function for the cytoplasm in the host's innate immunity by secreting inflammatory factors and promoting maturation, such as for interleukin-1β (IL-1β) and interleukin-18 (IL-18)(He et al., 2016a; Zhou et al., 2011). Seasonable activation of the NLRP3 inflammasome has a positive effect on the body; excessive activation of the NLRP3 inflammasome causes programmed cell death termed ‘pyroptosis’ via the secretion of large amounts of proinflammatory cytokines and triggers a highly inflammatory form of caspase-1(Van Opdenbosch and Lamkanfi, 2019). There are usually two signal modes of NLRP3 inflammasome activation: the host's crucial immune response to external stimuli regulates the main checkpoints of the two signalling pathways(He et al., 2016a; Swanson et al., 2019). A recent explosion in studies on the regulation of the interaction between lncRNAs and the NLRP3 inflammasome in the activation of inflammatory pathways has brought to the forefront new insights into the prophylaxis, diagnosis, and treatment of various diseases(Bordon, 2019; Haque et al., 2020; Ma et al., 2019; Nie et al., 2019; Song et al., 2019a; Zhang et al., 2020a). Our article reviews recent high-throughput studies of the relationship between lncRNAs and NLRP3 inflammasome under different conditions.
Section snippets
The molecular structure and the role of lncRNAs
LncRNAs are poorly conserved and lack complete ORFs, longer than 200 nt(Quinn and Chang, 2016). As with messenger RNA (mRNA), transcription for most lncRNAs is mediated by RNA polymerase II; this transcription mechanism is completed by 5-terminal capping, Pol II occupancy, histone modifications, and polyadenylation. RNA polymerase III can mediate part of lncRNA transcription(Pagano et al., 2007). The traditional understanding regards lncRNAs as having no coding function and being more poorly
The regulatory relationship between lncRNAs and NLRP3 inflammasomes
The central rule of molecular biology is the transcription of genetic information from DNA to RNA and its translation into proteins. LncRNAs have been found to function in inflammation and immune-related cells, such as T lymphocytes, B lymphocytes, and dendritic cells (DCS)(Geng and Tan, 2016). LncRNAs participate in all cell function stages, including cell differentiation, development, metabolism, and immunity(Wu et al., 2015a). Numerous high-quality research data sets have indicated that
LncRNAs and NLRP3 in inflammatory diseases
The biological and clinical roles of lncRNAs and the NLRP3 inflammasome have recently been studied extensively in the inflammatory response and inflammatory cascade reaction(Haque et al., 2020; He et al., 2019). Zhang et al. speculated that the lncRNA Neat1 regulated activation of inflammasomes by assembling NLRP3, NLRC4, and AIM2 components and promoted IL-1β induced pyroptosis by stabilizing the mature caspase-1 in mouse macrophages(Zhang et al., 2019b). In the common pathways of various
Conclusion
In summary, the interaction of the NLRP3 inflammasome and lncRNAs has been most intensively investigated in various diseases, including cancer, pyroptosis, Alzheimer's disease, neuroinflammation, cardiovascular diseases, I/R injury, and inflammatory diseases. There is increasing evidence that lncRNAs mainly regulate the NLRP3 inflammasome associated with pathophysiological processes pre- and posttranscription. We still know very little about their precise regulatory mechanisms during the
Author contribution statement
Author: Deqiang Luo Contribution: 1. Design research direction 2. Write papers. Author: Fen Liu Contribution: 1. Collect references and analysis 2. Review and revise the papers.
Author:Wenqiang Tao Contribution:Review and revise the papers.
Author:Rui Xiao Contribution:Review and revise the papers Author:Jianguo Zhang Contribution:Review and edit the article. Author:Qiang Shao Contribution:Review and revise the papers.
Author:Wei Dai Contribution:Review and revise the papers.
Author: Keqian Qian
Funding
The study accepts the National Natural Science Foundation of China (81560306 and 81460292) and Graduate Student Innovation Special Fund Project of Jiangxi Province (YC2020-B033).
Ethical approval and consent to participate
This article does not involve any studies with patients or animals performed by any of the authors.
Declaration of Competing Interest
There is no conflict of interest in this study. All authors declare that they have no conflict of interest.
Acknowledgments
We are grateful to the personnel of all the hospitals who participated in this article for their support during design and revision. This work was funded by a grant from The First Affiliated Hospital of Nanchang University.
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