Littérature scientifique sur le sujet « NcRNAs, lncRNAs, miRNA, immunity »

Abstract Non-coding RNAs (ncRNAs) comprise a diverse range of biologically functional RNA species that include long ncRNAs (lncRNA) and short ncRNAs such as piwi-interacting RNAs (piRNA) and microRNAs (miRNA). These ncRNAs are capable of regulating gene expression via distinct mechanisms depending on their structure---miRNAs bind specific messenger RNAs (mRNA) to block translation while lncRNAs tend to bind chromatin to modify chromatin states to interfere with gene expression. NcRNAs have been identified in numerous diseases as having altered expression. To further elucidate the role of ncRNAs in immunity, we conducted a screen of lncRNA expression in the interleukin-10 knockout mouse (IL-10−/−) model of intestinal inflammation. This screen identified several candidate lncRNAs with dysregulated expression. Importantly, our data demonstrate that Malat1 and Hoxa11as expression was significantly decreased in mice with severe intestinal pathology. These results suggest that an association exists between these lncRNAs and the progression of disease in the IL-10−/− mouse model of colitis.

Immunological diseases, including asthma, autoimmunity and immunodeficiencies, affect a growing percentage of the population with significant unmet medical needs. As we slowly untangle and better appreciate these complex genetic and environment-influenced diseases, new therapeutically targetable pathways are emerging. Non-coding RNA species, which regulate epigenetic, transcriptional and translational responses are critical regulators of immune cell development, differentiation and effector function, and may represent one such new class of therapeutic targets. In this review we focus on type-2 immune responses, orchestrated by TH2 cell-derived cytokines, IL-4, IL-5 and IL-13, which stimulate a variety of immune and tissue responses- commonly referred to as type-2 immunity. Evolved to protect us from parasitic helminths, type-2 immune responses are observed in individuals with allergic diseases, including Asthma, atopic dermatitis and food allergy. A growing number of studies have identified the involvement of various RNA species, including microRNAs (miRNA) and long non-coding (lncRNA), in type-2 immune responses and in both clinical and pre-clinical disease settings. We highlight these recent findings, identify gaps in our understanding and provide a perspective on how our current understanding can be harnessed for novel treat opportunities to treat type-2 immune-mediated diseases.

Disease has been a major concern in the rice-growing sector, resulting in significant losses and compromised food security. To combat disease, plants have devised various defense strategies. Initial works in understanding plant–pathogen interactions were focused on discovering resistance and pathogenicity genes, as well as analyzing the functions of these genes in the host defense. Later, researchers discovered that regulatory elements, such as transcription factors, were essential players in modulating plant defenses. As the depth of research and knowledge in this field increased, non-coding RNA (ncRNA) were discovered to play key functions in plant immunity. In this review, we explore the contribution and interaction of microRNAs (miRNAs), long ncRNAs (lncRNAs), and small interfering RNAs (siRNAs) in controlling the rice immune response. The role and the interaction between ncRNAs and their targets have been discussed in detail. We believe that this information will be beneficial in disease resistance breeding of rice.

Cancer immunology research has mainly focused on the role of protein-coding genes in regulating immune responses to tumors. However, despite more than 70% of the human genome is transcribed, less than 2% encodes proteins. Many non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have been identified as critical regulators of immune cell development and function, suggesting that they might play important roles in orchestrating immune responses against tumors. In this review, we summarize the scientific advances on the role of ncRNAs in regulating adaptive tumor immunity, and discuss their potential therapeutic value in the context of cancer immunotherapy.

The liver is well known as the center of glucose and lipid metabolism in the human body. It also functions as an immune organ. Previous studies have suggested that liver nonparenchymal cells are crucial in the progression of NAFLD. In recent years, NAFLD’s threat to human health has been becoming a global issue. And by far, there is no effective treatment for NAFLD. Liver nonparenchymal cells are stimulated by lipid antigens, adipokines, or other factors, and secreted immune factors can alter the expression of key proteins such as SREBP-1c, ChREBP, and PPARγ to regulate lipid metabolism, thus affecting the pathological process of NAFLD. Interestingly, some ncRNAs (including miRNAs and lncRNAs) participate in the pathological process of NAFLD by changing body fat homeostasis. And even some ncRNAs could regulate the activity of HSCs, thereby affecting the progression of inflammation and fibrosis in the course of NAFLD. In conclusion, immunotherapy could be an effective way to treat NAFLD.

Esophageal squamous cell carcinoma (ESCC) is a highly prevalent tumor and is associated with ethnicity, genetics, and dietary intake. Non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) have been reported as functional regulatory molecules involved in the development of many human cancers, including ESCC. Recently, several ncRNAs have been detected as oncogenes or tumor suppressors in ESCC progression. These ncRNAs influence the expression of specific genes or their associated signaling pathways. Moreover, interactions of ncRNAs are evident in ESCC, as miRNAs regulate the expression of lncRNAs, and further, lncRNAs and circRNAs function as miRNA sponges to compete with the endogenous RNAs. Here, we discuss and summarize the findings of recent investigations into the role of ncRNAs (miRNAs, lncRNAs, and circRNAs) in the development and progression of ESCC and how their interactions regulate ESCC development.

ncRNAs (non-coding RNAs) are implicated in a wide variety of cellular processes, including the regulation of gene expression. In the present chapter we consider two classes of ncRNA: miRNAs (microRNAs) which are post-transcriptional regulators of gene expression and lncRNAs (long ncRNAs) which mediate interactions between epigenetic remodelling complexes and chromatin. Mutation and misexpression of ncRNAs have been implicated in many disease conditions and, as such, pharmacological modulation of ncRNAs is a promising therapeutic approach. miRNA activity can be antagonized with antisense oligonucleotides which sequester or degrade mature miRNAs, and expressed miRNA sponges which compete with target transcripts for miRNA binding. Conversely, synthetic or expressed miRNA mimics can be used to treat a deficiency in miRNA expression. Similarly, conventional antisense technologies can be used to silence lncRNAs. Targeting promoter-associated RNAs with siRNAs (small interfering RNAs) results in recruitment of chromatin-modifying activities and induces transcriptional gene silencing. Alternatively, targeting natural antisense transcripts with siRNAs or antisense oligonucleotides can abrogate endogenous epigenetic silencing leading to transcriptional gene activation. The ability to modulate gene expression at the epigenetic level presents exciting new opportunities for the treatment of human disease.

The morbidity and mortality of myocardial ischemia–reperfusion injury (MIRI) have increased in modern society. Noncoding RNAs (ncRNAs), including lncRNAs, circRNAs, piRNAs and miRNAs, have been reported in a variety of studies to be involved in pathological initiation and developments of MIRI. Hence this review focuses on the current research regarding these ncRNAs in MIRI. We comprehensively introduce the important features of lncRNAs, circRNAs, piRNA and miRNAs and then summarize the published studies of ncRNAs in MIRI. A clarification of lncRNA–miRNA–mRNA, lncRNA–transcription factor–mRNA and circRNA–miRNA–mRNA axes in MIRI follows, to further elucidate the crucial roles of ncRNAs in MIRI. Bioinformatics analysis has revealed the biological correlation of mRNAs with MIRI. We provide a comprehensive perspective for the roles of these ncRNAs and their related networks in MIRI, providing a theoretical basis for preclinical and clinical studies on ncRNA-based gene therapy for MIRI treatment.

AbstractBeyond the most crucial roles of RNA molecules as a messenger, ribosomal, and transfer RNAs, the regulatory role of many non-coding RNAs (ncRNAs) in plant biology has been recognized. ncRNAs act as riboregulators by recognizing specific nucleic acid targets through homologous sequence interactions to regulate plant growth, development, and stress responses. Regulatory ncRNAs, ranging from small to long ncRNAs (lncRNAs), exert their control over a vast array of biological processes. Based on the mode of biogenesis and their function, ncRNAs evolved into different forms that include microRNAs (miRNAs), small interfering RNAs (siRNAs), miRNA variants (isomiRs), lncRNAs, circular RNAs (circRNAs), and derived ncRNAs. This article explains the different classes of ncRNAs and their role in plant development and stress responses. Furthermore, the applications of regulatory ncRNAs in crop improvement, targeting agriculturally important traits, have been discussed.

Non-coding RNAs (ncRNAs) comprise a diversity of RNA species, which do not have the potential to encode proteins. Non-coding RNAs include two classes of RNAs, namely: short regulatory ncRNAs and long non-coding RNAs (lncRNAs). The short regulatory RNAs, containing up to 200 nucleotides, include small RNAs, such as microRNAs (miRNA), short interfering RNAs (siRNAs), piwi-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs). The lncRNAs include long antisense RNAs and long intergenic RNAs (lincRNAs). Non-coding RNAs have been implicated as master regulators of several biological processes, their expression being strictly regulated under physiological conditions. In recent years, particularly in the last decade, substantial effort has been made to investigate the function of ncRNAs in several human diseases, including cancer. Glioblastoma is the most common and aggressive type of brain cancer in adults, with deregulated expression of small and long ncRNAs having been implicated in onset, progression, invasiveness, and recurrence of this tumor. The aim of this review is to guide the reader through important aspects of miRNA and lncRNA biology, focusing on the molecular mechanism associated with the progression of this highly malignant cancer type.

Nel corso degli ultimi decenni, sempre più studi hanno dimostrato che la maggior parte del genoma dà origine a molecole di RNA non codificanti per proteine, ma capaci di influenzare, a livello epigenetico, l’espressione genica (ncRNA). Le due principali tipologie di ncRNA, gli RNA lunghi non-codificanti (lncRNA) e i microRNA (miRNA), hanno un ruolo centrale nella regolazione di diversi processi fisiologici e patologici. Nonostante la funzione di lncRNA e miRNA sia oggetto di molteplici studi, molti dei meccanismi molecolari che governano la loro espressione e la loro funzione nella regolazione della risposta immunitaria rimangono ancora da chiarire. Sulla base di queste premesse, questo studio ha lo scopo di identificare e caratterizzare il ruolo dei ncRNA nella regolazione delle funzioni di cellule immunitarie in situazioni sia fisiologiche che patologiche. In particolare, lo studio si è articolato in modo da perseguire tre obiettivi principali:(A) Identificazione e caratterizzazione del ruolo dei lncRNA in monociti e neutrofili umani in risposta all’attivazione del TLR4;(B) Identificazione e caratterizzazione del ruolo dei lncRNA in monociti purificati da pazienti affetti da Sclerosi Sistemica (SSc);(C) Analisi dell'espressione di miRNA nella leucemia a Grandi Linfociti granulati (LGLL).(A) Questo studio ha dimostrato che l’attivazione di monociti e neutrofili da parte del lipopolisaccaride batterico (LPS) è in grado di indurre l'espressione dei lncRNA. In particolare abbiamo caratterizzato i lncRNA espressi in maniera cellulo-specifica. Un’analisi effettuata in silico ha inoltre evidenziato che i lncRNA identificati sono potenzialmente in grado di regolare diversi processi fisiologici di monociti e neutrofili, quali la produzione di citochine e chemochine, la morte cellulare, il rimodellamento della cromatina e la trasduzione del segnale. Infine, abbiamo caratterizzato la funzione di due lncRNA, LINC00085 e AC002480.3, dimostrando un loro ruolo nella regolazione dell’espressione del miR-99b e di IL-6.(B) La caratterizzazione dei lncRNA espressi in monociti è stato esteso alla SSc, una patologia in cui i monociti sono stati recentemente indicati come popolazione cellulare con un ruolo importante nella sua patogenesi. La SSc è una malattia autoimmune caratterizzata dallo sviluppo di un’ingravescente fibrosi cutanea e degli organi interni e da un’alterata risposta immunitaria caratterizzata anche da un aumento del numero di monociti. I risultati di questo studio hanno evidenziato che l’espressione dei lncRNA è alterata in tutti i sottotipi di SSc: non-cutaneous SSc (ncSSc), limited cutaneous (lcSSc) e diffuse cutaneous (dcSSc). Inoltre, abbiamo identificato identificare tre gruppi di lncRNA, specificamente modulati in ciascuna classe di SSc, che possono essere utilizzati come marcatori biologici dello sviluppo e della progressione della malattia. Infine, mediante analisi in silico abbiamo dimostrato che i lncRNA sono coinvolti nella regolazione di alcuni processi biologici fondamentali per lo sviluppo della SSc, come la differenziazione dei monociti in miofibroblasti e la regolazione di geni interferone-dipendenti che caratterizzano la patologia.(C) Nel terzo studio abbiamo analizzato il ruolo dei miRNA nella patogenesi della T-LGLL, una malattia linfoproliferativa cronica caratterizzata da un aumento del numero di T-LGL.I risultati ottenuti dimostrano che i livelli di espressione dei miRNA in T-LGL sono alterati rispetto ai linfociti T citotossici normali. In particolare, questo studio ha evidenziato una forte correlazione tra l’espressione dei miRNA stessi, il fenotipo dei T-LGL e i livelli di attivazione di STAT3.In sintesi, in questo studio abbiamo descritto che l'espressione dei lncRNA è modulata in monociti e neutrofili umani attivati da LPS. Inoltre, abbiamo identificato, per la prima volta, che i livelli di espressione dei ncRNA sono alterati in cellule immunitarie coinvolte nella patogenesi della SSc e della T-LGLL.
During past decades, genome-wide studies have revealed that mammalian genome is widespreadly transcribed and this led to the identification and isolation of novel classes of non-coding RNAs (ncRNAs) that influence gene expression by epigenetic mechanisms.The regulatory ncRNAs can be classified into long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) increasingly recognised to play a role in both physiological and pathological conditions. Despite the function of lncRNAs and miRNAs is the subject of intense studies, the molecular mechanism governing their expression and actions in immune cell function remains to be elucidated. Based on these premises, the purpose of this study is to provide a comprehensive identification and characterization of the role of ncRNAs in immune cell populations under both physiological and pathological conditions. In particular, the study is focused on three main goals:(A) Identification and characterization of the role of lncRNAs in resting and activated human monocytes and neutrophils;(B) Analysis of the expression of lncRNAs was extended to monocytes of patients affected by Systemic Sclerosis (SSc). In fact, several observations suggest that monocytes are likely to play a pathogenetic role in SSc disease;(C) Identification and characterization of the role of miRNAs in Large Granular Lymphocyte Leukaemia (LGLL).(A) The results of this study show that TLR4 activation is able to modulate the expression of lncRNAs in both monocytes and neutrophils. Most importantly, a subset of lncRNAs selectively expressed and modulated by LPS in a cell specific manner was identified. In silico analysis of the putative function of differentially expressed lncRNAs was performed, and suggests that lncRNAs regulate innate immune cells functions such as cytokines and chemokines biosynthesis, cell death, chromatin remodelling and signal transduction. Finally, we started to characterize the function of LINC00085 and AC002480.3. Although further studies must be performed in order to fully understand the role of these lncRNAs, our results indicate that LINC00085 controls the expression of miR-99b, while AC002480.3 has a role in the regulation of IL-6 production.(B) Monocytes have been recently indicated as crucial players in the pathogenesis of SSc. To identify the lncRNAs expressed and modulated in monocytes from SSc patients compared to healthy donors, RNA-seq analysis was performed. Our results show that all the progressive subset of SSc (ncSSc, lcSSc and dcSSc), are characterized by altered expression of lncRNAs in monocytes. Additionally, a detailed analysis of the expression levels of lncRNAs led to the identification of three groups of ncRNAs, specifically modulated in ncSSc rather than lcSS, or dcSSc and that can be used as biomarker for SSc development and progression. Finally, by performing in silico analysis of lncRNA function we show that they are involved in the regulation of key biological processes for the development of SSc, such as the differentiation from monocyte into myofibroblast, and the establishment of the interferon signature that characterizes the SSc.(C) The role of miRNAs in the pathogenesis of LGLL, was examined. By using high-throughput analysis, we initially characterized the profile of miRNAs expressed in T-LGLs, revealing a previously undescribed differential expression of miRNAs in T-LGL from leukemic patients compared to normal cytotoxic T lymphocytes. Interestingly, we identify a strong correlation among the miRNAs expression profiles, the T-LGL phenotype and the activation levels of STAT3.In summary, we have described that the expression of lncRNAs is modulated in LPS-activated human monocytes and neutrophils. In addition, our results show, for the first time, that ncRNA expression levels are deregulated in immune cells involved in the pathogenesis of SSc (monocytes) and T-LGLL. The results we have found suggest that these ncRNAs could be considered new biomarkers for SSc and T-LGLL.