Liver diseases are a significant global health issue, characterized by elevated levels of disorder and death. The substantial impact of ageing on liver diseases and their prognosis is evident. Multiple processes are involved in the ageing process, which ultimately leads to functional deterioration of this organ. The process of liver ageing not only renders the liver more susceptible to diseases but also compromises the integrity of other organs due to the liver's critical function in metabolism regulation. A growing body of research suggests that long non-coding RNAs (lncRNAs) play a significant role in the majority of pathophysiological pathways. They regulate gene expression through a variety of interactions with microRNAs (miRNAs), messenger RNAs (mRNAs), DNA, or proteins. LncRNAs exert a major influence on the progression of age-related liver diseases through the regulation of cell proliferation, necrosis, apoptosis, senescence, and metabolic reprogramming. A concise overview of the current understanding of lncRNAs and their potential impact on the development of age-related liver diseases will be provided in this mini-review.

Exploring the potential of BOLA3-DT as a diagnostic biomarker in prostate cancer.

Expression of the lncRNA BOLA3-DT was analyzed between normal and tumor samples in the GDC TCGA PRAD (Genomic Data Commons: The Cancer Genome Atlas Prostate Adenocarcinoma Collection) dataset. Disease progression-related clinicopathological parameters such as serum PSA level (ng/ml) and Gleason score were associated with the expression of BOLA3-DT using the same GDC TCGA PRAD dataset. To validate these findings, the expression of BOLA3-DT was checked in our sample set of 15 PCa (prostate cancer) and 15 BPH (benign hypertrophy of the prostate) patients.

In the GDC TCGA PRAD dataset, the expression of the lncRNA BOLA3-DT was significantly downregulated in prostate cancer tissue samples (n = 492) compared to adjacent normal (n = 52; p < 0.0001), and, there was a significant negative correlation between the expression of the lncRNA BOLA3-DT and the serum PSA level (p < 0.01). However, no significant association was found between the lncRNA BOLA3-DT expression and the Gleason score (p > 0.05). In this study, it was found that BOLA3-DT was downregulated in PCa tissue samples compared to BPH samples (p > 0.05). In the GDC TCGA PRAD dataset, it was revealed that BOLA3-DT could serve as an excellent diagnostic marker with a sensitivity of 86.9% and a specificity of 84.6% (AUC-0.916).

LncRNA BOLA3-DT, a novel long non-coding RNA, was found to be downregulated in prostate cancer. The expression of the lncRNA BOLA3-DT can serve as a diagnostic marker in prostate cancer.

Cells preserve and convey certain gene expression patterns to their progeny through the mechanism called epigenetic memory. Epigenetic memory, encoded by epigenetic markers and components, determines germline inheritance, genomic imprinting, and X chromosome inactivation. First discovered long non coding RNAs were implicated in genomic imprinting and X-inactivation and these two phenomena clearly demonstrate the role of lncRNAs in epigenetic memory regulation. Undoubtedly, lncRNAs are well-suited for regulating genes in close proximity at imprinted loci. Due to prolonged association with the transcription site, lncRNAs are able to guide chromatin modifiers to certain locations, thereby enabling accurate temporal and spatial regulation. Nevertheless, the current state of knowledge regarding lncRNA biology and imprinting processes is still in its nascent phase. Herein, we provide a synopsis of recent scientific advancements to enhance our comprehension of lncRNAs and their functions in epigenetic memory, with a particular emphasis on genomic imprinting and X chromosome inactivation, thus gaining a deeper understanding of the role of lncRNAs in epigenetic regulatory networks.

The occurrence of diabetic kidney disease (DKD), a critical microvascular issue in diabetes, is progressively on the rise. In recent years, long noncoding RNAs (lncRNAs) have garnered considerable attention as a novel and critical layer of biological regulation. Our knowledge regarding the roles and underlying mechanisms of lncRNAs in various diseases, including DKD, continues to evolve. Similarly, microRNAs (miRNAs), which are small noncoding RNAs, have been recognized as crucial contributors to cellular processes and disease pathogenesis. Emerging studies have highlighted the complex interactions between lncRNAs and miRNAs, particularly in the context of DKD, underscoring their importance in complex human diseases. Renal intrinsic cell damage is an important cause of inducing DKD. Persistent high glucose stimulation leads to remodeling of renal intrinsic cells and a cascade of pathological changes. This article aims to review recent literature on the lncRNAs-mediated regulation of miRNAs affecting renal intrinsic cells in DKD and to propose novel molecular-level therapeutic strategies for DKD. Through in-depth investigation of this dynamic molecular interaction, we can gain a profound understanding of the potential mechanisms underlying diabetic nephropathy, potentially identifying new targets for therapeutic intervention and paving the way for personalized and effective treatments.

Epigenetics, the study of heritable changes in gene expression that do not involve alterations to the deoxyribonucleic acid (DNA) sequence, plays a pivotal role in cellular function, development, and aging. This review explores key epigenetic mechanisms, including DNA methylation (DNAm), histone modifications, chromatin remodeling, RNA-based regulation, and long-distance chromosomal interactions. These modifications contribute to cellular differentiation and function, mediating the dynamic interplay between the genome and environmental factors. Epigenetic clocks, biomarkers based on DNAm patterns, have emerged as powerful tools to measure biological age and predict health span. This article highlights the evolution of epigenetic clocks, from first-generation models such as Horvath's multi-tissue clock to advanced second- and third-generation clocks such as DNAGrimAge and DunedinPACE, which incorporate biological parameters and clinical biomarkers for precise age estimation. Moreover, the role of epigenetics in aging and age-related diseases is discussed, emphasizing its impact on genomic stability, transcriptional regulation, and cellular senescence. Epigenetic dysregulation is implicated in cancer, genetic disorders, and neurodegenerative diseases, making it a promising target for therapeutic interventions. The reversibility of epigenetic modifications offers hope for mitigating age acceleration and enhancing health span through lifestyle changes and pharmacological approaches.

In this study, we employed a total of eight distinct modifications of histone proteins (H3K23ac, H3K27me3, H3K36me3, H3K4me3, H3K9ac, H3K9me3, H4K12ac, and H4K20me1) to discern the various chromatin colors encompassing lncRNA genes in both mature and immature gonads of the human parasite Schistosoma mansoni. Our investigation revealed that these chromatin colors exhibit a tendency to aggregate based on the similarities in their metagene shapes, leading to the formation of less than six distinct clusters. Moreover, these clusters can be further grouped according to their resemblances by shape, which are co-linear with specific regions of the genes, and potentially associated with transcriptional stages.

Chemoresistance leads to poor outcomes of patients with gastric cancer (GC). Long non-coding RNAs (lncRNAs) have been demonstrated as novel gene modulators in various carcinomas and chemoresistance. Our study aimed to investigate the role and underlying modulatory mechanism of lncRNA MATN1-AS1 in GC chemoresistance. CCK-8, flow cytometry, and Transwell assays were performed to explore the influence of the MATN1-AS1/microRNA (miR)-518b/zinc finger protein 281 (ZNF281) axis on the half inhibition concentration (IC50) to oxaliplatin (OXA), apoptosis, migration, and invasion of OXA-resistant GC cells. Dual-luciferase reporter assay was conducted to confirm the target association between miR-518b and MATN1-AS1 (or ZNF281). Xenograft mouse models were established to confirm the role of MATN1-AS1 silencing in vivo. The expression of MATN1-AS1, miR-518b, ZNF281, and multidrug resistance-related genes was detected through RT-qPCR and western blotting. MATN1-AS1 expression was upregulated in OXA-resistant GC tissues and cell lines versus OXA-sensitive tissues and parental cell lines. MATN1-AS1 depletion significantly inhibited the IC50 value of OXA, cell migration, invasion, and drug resistance but promoted cell apoptosis in OXA-resistant GC cells. Additionally, MATN1-AS1 upregulated ZNF281 expression by sponging miR-518b in OXA-resistant GC cells. Inhibiting miR-518b or overexpressing ZNF281 antagonized the effects of MATN1-AS1 silencing on OXA resistance of GC cells. Upregulation of ZNF281 abrogated the suppressive effects of miR-518b overexpression on OXA resistance of GC cells. Moreover, MATN1-AS1 knockdown suppressed tumor growth, OXA resistance, and Ki-67 expression in xenograft mouse models. MATN1-AS1 promotes OXA resistance of GC cells by enhancing ZNF281 expression via sequestration of miR-518b, shedding new light on the chemoresistance of GC.

Small nucleolar RNAs (snoRNAs) play essential roles in various cellular processes, and their associations with diseases are increasingly recognized. Identifying these snoRNA-disease relationships is critical for advancing our understanding of their functional roles and potential therapeutic implications. This work presents a novel approach, called GL4SDA, to predict snoRNA-disease associations using Graph Neural Networks (GNN) and Large Language Models. Our methodology leverages the unique strengths of heterogeneous graph structures to model complex biological interactions. Differently from existing methods, we define a set of features able to capture deeper information content related to the inner attributes of both snoRNAs and diseases and design a GNN model based on highly performing layers, which can maximize results on this representation. We consider snoRNA secondary structures and disease embeddings derived from large language models to obtain snoRNAs and disease node features, respectively. By combining structural features of snoRNAs with rich semantic embeddings of diseases, we construct a feature-rich graph representation that improves the predictive performance of our model. We evaluate our approach using different architectures that exploit the capabilities of many graph convolutional layers and compare the results with three other state-of-the-art graph-based predictors. GL4SDA demonstrates improved scores in link prediction tasks and demonstrates its potential implication as a tool for exploring snoRNA-disease relationships. We also validate our findings through biological case studies about cancer diseases, highlighting the practical application of our method in real-world scenarios and obtaining the most important snoRNA features using explainable artificial intelligence methods.

Long noncoding RNAs (lncRNAs) play numerous roles in cellular biology and alterations in lncRNA expression profiles have been implicated in a variety of cancers. Here, we identify and characterize a lncRNA, TRIM28 Interacting DNA damage repair Enhancing Noncoding Transcript (TRIDENT), whose expression is induced upon epithelial growth factor receptor (EGFR) activation, and which exerts pro-oncogenic functions in EGFR-driven non-small cell lung cancer. Knocking down TRIDENT leads to decreased tumor-cell proliferation in both in vitro and in vivo model systems and induces sensitization to chemotherapeutic drugs. Using ChIRP-MS analysis we identified TRIM28 as a protein interactor of TRIDENT. TRIDENT promotes phosphorylation of TRIM28 and knocking down TRIDENT leads to accumulation of DNA damage in cancer cells via decreased TRIM28 phosphorylation. Altogether, our results reveal a molecular pathway in which TRIDENT regulates TRIM28 phosphorylation to promote tumor cell growth and drug resistance. Our findings suggest that TRIDENT can be developed as a biomarker or therapeutic target for EGFR mutant non-small cell lung cancer.

The role of long non-coding RNAs (lncRNAs) and their nearby messenger RNAs (mRNAs) in systemic lupus erythematosus (SLE) pathogenesis is not well understood.

High-throughput sequencing was utilized to analyze PBMCs obtained from SLE patients. Subsequently, we conducted differential analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and verification through quantitative real-time PCR (qRT-PCR). Additionally, qRT-PCR was used to analyze the levels of lncRNAs or mRNAs in transfected Raji cells.

We identified 419 differentially expressed (DE) lncRNAs and their 337 nearby DE mRNAs in SLE patients. More than 67% of the DE lncRNAs were lincRNAs and intronic_lncRNAs. The most significantly regulated nearby mRNAs in SLE patients were LTF and CIRBP, potentially involved in recurrent infection and photosensitivity. GO analysis revealed upregulation of the immune effector process term, with genes such as C1qA, C1qC, C1qB, NLRP3, and CXCL6 participating in this term and the upregulated pertussis signaling pathway. Analysis of the nearby coding genes of 88 lincRNAs indicated that XLOC_185773 had the highest number of nearby encoding genes and was negatively correlated with peripheral blood lymphocyte counts, potentially regulating HARS. Furthermore, LNC_005556, an antisense DE lncRNA, was negatively correlated with lupus nephritis occurrence and may regulate the upregulated IGLL5 in patients.

The current study provides insights into the dysregulation of lncRNAs and nearby mRNAs in SLE, highlighting potential key players in the pathogenesis of the disease.

In mammals, long non-coding RNAs (lncRNAs) play a regulatory role in gene expression, contribute to immune responses, and aid in pathogen elimination, primarily through interactions with RNA-binding proteins (RBPs). However, the role of lncRNAs in fish innate immunity and their interaction with RBPs remains uncertain. To investigate the immunomodulatory role of lncRNAs in Megalobrama amblycephala, we identified the novel lncRNA MSTRG.59348.1 and examined its function in the innate immune response to Aeromonas hydrophila infection. Localization studies in hepatocytes revealed that MSTRG.59348.1 is primarily located in the nucleus, suggesting its potential involvement in gene regulation, possibly through chromatin modification or other nuclear processes. The expression of MSTRG.59348.1 was significantly up-regulated after lipopolysaccharide (LPS) stimulation in liver cells. RNA-seq analysis of muscle cells revealed that genes differentially expressed following MSTRG.59348.1 overexpression were enriched in immune pathways. MSTRG.59348.1 overexpression significantly inhibited the expression of sting and ifn, and significantly up-regulated muscle cell viability and promoted cell proliferation by targeting sting, ifn, nf-κb1, and bcl2. Screening by RNA pull-down and mass spectrometry identified 57 RBPs interacting with MSTRG.59348.1, with functions enriched in immune pathways. Our results suggest that MSTRG.59348.1 plays a crucial regulatory role in fish antibacterial response, marking it as a significant subject for future research in innate immunity.

Tumor metastasis regulated by multiple complicated pathways is closely related to variations in the tumor microenvironment. Exosomes can regulate the tumor microenvironment through various mechanisms. Exosomes derived from tumor cells carry a variety of substances, including long non-coding RNAs (lncRNAs), play important roles in intercellular communication and act as critical determinants influencing tumor metastasis. In this review, we elaborate on several pivotal processes through which lncRNAs regulate tumor metastasis, including the regulation of epithelial‒mesenchymal transition, promotion of angiogenesis and lymphangiogenesis, enhancement of the stemness of tumor cells, and evasion of immune clearance. Additionally, we comprehensively summarized a diverse array of potential tumor-derived exosomal lncRNA biomarkers to facilitate accurate diagnosis and prognosis in a clinical setting.

Alzheimer's disease (AD), a diverse neurodegenerative disease, is the leading cause of dementia, accounting for 60-80 % of all cases. The pathophysiology of Alzheimer's disease is unknown, and there is no cure at this time. Recent developments in transcriptome-wide profiling have led to the identification of a number of non-coding RNAs (ncRNAs). Among these, long non-coding RNAs (lncRNAs)-long transcripts that don't seem to be able to code for proteins-have drawn attention because they function as regulatory agents in a variety of biological processes. Recent research suggests that lncRNAs play a role in the pathogenesis of Alzheimer's disease by modulating tau hyperphosphorylation, amyloid production, synaptic impairment, neuroinflammation, mitochondrial dysfunction, and oxidative stress, though their precise effects on the disorder are unknown. The biology and modes of action of the best-characterized lncRNAs in AD will be outlined here, with an emphasis on their possible involvement in the pathophysiology of the disease. As lncRNAs may offer prospective prognostic/diagnostic biomarkers and therapeutic targets for the treatment of AD, a greater comprehension of the molecular processes and the intricate network of interactions in which they are implicated could pave the way for future research.

Emerging evidence indicates that long non-coding RNAs (lncRNAs) play a regulatory role in plant response to environmental stresses. Seed germination is a complex physiological process modulated by many environmental and phytohormonal cues. However, how lncRNAs and phytohormones interactively regulate the response of seed germination to salt stress remain largely unknown. Here, we functionally characterized a salt-responsive lncRNA from legume species Medicago truncatula, referred to as MtCIR2, in response to salt stress during seed germination by heterologously expressing MtCIR2 in Arabidopsis in which none such homologous sequence was detected. Expressing MtCIR2 in Arabidopsis rendered the seed germination more sensitive to salt stress. We further evaluated whether and how abscisic acid (ABA) and gibberellin (GA) were involved in the MtCIR2-mediated seed germination in response to salt stress. We found that expression of MtCIR2 led to an increase in endogenous ABA concentration and a decrease in overall GA concentration due to enhanced expression of ABA catabolic gene CYP707A2 and suppressed expression of the genes of GA20ox1, GA20ox2, and GA20ox5 involved in GA synthesis under salt stress, respectively. The MtCIR2-dependent enhanced endogenous ABA and reduced endogenous GA concentrations in seeds resulted in greater suppression of seed germination in transgenic seeds than in wild-type seeds when exposed to salt stress. These findings highlight a regulatory role of lncRNAs in response to salt stress during seed germination.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an inflammatory response arising from lung and systemic injury with diverse causes and associated with high rates of morbidity and mortality. To date, no fully effective pharmacological therapies have been established and the relevant underlying mechanisms warrant elucidation, which may be facilitated by multi‑omics technology. The present review summarizes the application of multi‑omics technology in identifying novel diagnostic markers and therapeutic strategies of ALI/ARDS as well as its pathogenesis.

Diabetes mellitus (DM) is a chronic metabolic disorder and one of the most significant global health burdens worldwide. Key pathophysiological mechanisms underlying its onset and associated complications include hyperglycemia-related stresses, such as oxidative stress and endoplasmic reticulum stress (ER stress). Long non-coding RNAs (lncRNAs), defined as RNA transcripts longer than 200 nucleotides and lacking protein-coding capacity, play crucial roles in various biological processes and have emerged as crucial regulators in the pathogenesis of diabetes. This review provides a comprehensive overview of lncRNA biogenesis and its functional roles, emphasizing recent findings that link stress-related lncRNAs to diabetic pathology and complications. Also, we discuss how lncRNAs influence diabetes and its complications by modulating pathways involved in cell death, proliferation, inflammation, and fibrosis, which contribute to pancreatic β cell dysfunction, insulin resistance, diabetic nephropathy, and retinopathy. By analyzing current research, we aim to enhance understanding of lncRNA involvement in diabetes while identifying potential therapeutic targets and guiding future research directions to elucidate the complex mechanisms underlying this pervasive condition.

A large fraction of the human genome is transcribed in RNA molecules that do not encode for proteins but that do have a crucial role in regulating almost every level of gene expression and, thus, define the specific phenotype of each cell. These non-coding RNAs include well-characterized microRNAs and thousands of less-defined longer transcripts, named long non-coding RNAs. Both types markedly affect the onset and the progression of numerous pathologies, ranging from cancer to vascular and neuro-degenerative diseases. In recent years, a substantial effort has been made to design drugs targeting ncRNAs, and promising advancements have been produced from micro-RNA mimics and inhibitors. Each ncRNA controls several targets, and the overall effect of its inhibition or overexpression depends on the function of the set of genes it regulates. Therefore, in selecting the most appropriate target, and predicting the final outcome of ncRNA-based therapies, it is crucial to have and utilize detailed and accurate knowledge of their functional interactions. In this review, I recapitulate the principal resources which collect information on microRNA and lncRNA networks, focusing on the non-homogeneity of the data that result from disparate approaches. I highlight the role of RNA identifiers and interaction evidence standardization in helping the user to filter and integrate data derived from different databases in a reliable functional web of regulative relations.

High expression of the myeloid master ETS transcription factor PU.1 drives the development of monocyte/macrophage (Mono/MΦ), a crucial cellular component of the innate immune system. Disruptions in normal expression patterns of PU.1 are linked to a variety myeloid malignancy and immune diseases. It is evidenced that PU.1 binds to and modulates enhancers of several myeloid genes. While noncoding RNAs transcribed from noncoding genes at the enhancers are increasingly reported to be involved in enhancer regulation, the crosstalk between PU.1 and noncoding RNAs in enhancer-mediated myeloid gene regulation in Mono/MΦ differentiation and immune response has not been systematically investigated. In this study, we interrogated the PU.1-mediated transcriptome and cistrome with our comprehensive collection of putative and verified enhancers. Among a repertoire of noncoding genes present at PU.1-bound enhancers, we discovered that PU.1 acts as a potent transcription factor inducer of the noncoding RNA LOUP , which we previously identified as an RNA inducer of PU.1. The genomic region within the LOUP locus occupied by PU.1 is characterized by the epigenetic features of a myeloid-specific super-enhancer. Targeted disruption of the PU.1-binding motifs resulted in the downregulation of LOUP promoter activity. Depletion of LOUP reduced the expression of Mono/MΦ cell markers as well as the transcriptional program associated with Mono/MΦ differentiation Mono/MΦ innate defense mechanisms, including phagocytosis, antimicrobial activity, and chemoattractant cytokine production. LOUP induces Mono/MΦ phagocytic activities. Collectively, our findings indicate that PU.1 and enhancer RNA LOUP are biomolecular components of an unidentified feed-forward loop that promotes their mutual expression, contributing to Mono/MΦ differentiation and innate immune functions. The identification of the PU.1/ LOUP regulatory circuit provides valuable insights into the mechanisms underlying cell-type and gene-specific enhancer activity and Mono/MΦ biology, as well as significant implications for advancing our understanding of immune diseases and myeloid malignancies.

Accurate identification of ncRNA-protein interactions (NPIs) is critical for understanding various cellular activities and biological functions of ncRNAs and proteins. Many sequence- and/or structure- and graph-based computational approaches have been developed to identify NPIs from large-scale ncRNA and protein data in a high-throughput manner. However, many sequence- and/or structure- and graph-based computational approaches often ignore either the topological information in NPIs or the influence of other molecule networks on NPI prediction. In this work, we propose NPI-HGNN, an end-to-end graph neural network (GNN)-based approach for the identification of NPIs from a large heterogeneous network, consisting of the ncRNA-protein interaction network, the ncRNA-ncRNA similarity network, and the protein-protein interaction network. To our knowledge, NPI-HGNN is the first GNN-based predictor that integrates related heterogeneous networks for NPI prediction. Experiments on five benchmarking datasets demonstrate that NPI-HGNN outperformed several state-of-the-art sequence- and/or structure- and graph-based predictors. In addition, we showcased the prediction power of NPI-HGNN by identifying 12 interacting ncRNAs of the pre-mRNA 3' end processing protein, which indicates the effectiveness of the proposed model. The source code of NPI-HGNN is freely available for academic purposes at https://github.com/zhangxin11111/NPI-HGNN .

Intramuscular fat (IMF) content is a key indicator of yak meat quality. This study aimed to identify lncRNAs that regulate IMF deposition in yaks. Three male calf yaks (3 months) and three male adult yaks (3 years) were used in the current study. After slaughter, the tissue morphology of the longissimus dorsi (LD) muscle was assessed using a cry-sectioning technique and differentially expressed lncRNAs and mRNAs (DELs and DEMs) were identified using RNA-Seq technology. The diameter and volume of fat droplets were significantly larger and bigger, respectively, in adults than in calves (P < 0.001). A total of 37,790 genes and 16,400 lncRNAs that regulate fat deposition were identified. Among them, 2327 mRNAs and 474 lncRNAs were differentially expressed between calves and adult yaks. DEGs stearoyl-CoA desaturase (SCD), fatty acid synthase (FASN), fatty acid binding protein 4 (FABP4) and fibronectin 1 (FN1) and DELs MSTRG.15795.4 and MSTRG.35028.6 were screened. The enrichment and pathway analysis regulated by the DMEs and DELs were predicted. We found significantly enriched biological processes and pathways involved in fat deposition, including the biosynthesis of unsaturated fatty acids, fatty acid biosynthesis, fatty acid elongation, and the mTOR signaling pathway. Co-expression network of the DELs and related genes, including MSTRG.10268.1-placenta associated 8 (PLAC8), MSTRG.16223.1-galectin 3 (LGALS3), MSTRG.34732.1-glycerol-3-phosphate acyltransferase, mitochondrial (GPAM), MSTRG.11907.11-fibroblast growth factor 1 (FGF1), MSTRG.34342.1-lipase A, lysosomal acid type (LIPA), and MSTRG.1667.2-integrin subunit beta 2 (ITGB2) was constructed. RT-qPCR verified the sequence results. The molecular regulatory mechanisms of lncRNAs on intramuscular fat deposition in yak were further explored.

Long non-coding RNAs (lncRNAs) are RNA molecules exceeding 200 nucleotides in length. Recent studies have demonstrated their involvement in regulating gene expression and various biological processes. Among these, myogenesis and lipogenesis are particularly important because of their direct effects on muscle development and fat deposition in farm animals. These processes are crucial for determining meat quality, growth rates, and overall economic value in animal husbandry. Although the specific mechanisms through which lncRNAs influence these pathways are still under investigation, further research into their roles in muscle and fat development is crucial for optimizing farm animal breeding strategies. Here, we review the characteristics of lncRNAs, including their biogenesis, localization, and structures, with a particular focus on their association with myogenesis and adipogenesis. This review seeks to establish a theoretical foundation for enhancing farm animal production. In particular, focusing on lncRNAs may reveal how these molecules can enhance the economic traits of farm animals, thereby contributing to the optimization of farm animal breeding processes.

Long non-coding RNAs (lncRNAs) have emerged as essential regulators of gene expression, significantly influencing various biological processes. Approximately half of all lncRNAs are classified as long intergenic non-coding RNAs (lincRNAs), which are situated among coding genes. Recent studies have documented the role of lincRNAs in the pathogenesis of lung diseases, including lung cancer, pulmonary fibrosis, and pulmonary arterial hypertension. These lincRNAs can modulate gene expression through various mechanisms, including epigenetic modifications, transcriptional regulation, and post-transcriptional regulation. By functioning as competing endogenous RNAs (ceRNAs), lincRNAs can affect the activity of microRNAs (miRNAs) and their corresponding target genes. This review delves into the intricate mechanisms by which lincRNAs contribute to the development and progression of various lung diseases. Furthermore, it discusses the potential of lincRNAs as therapeutic targets.

Investigating whether mechanosensitive lncRNA H19 can directly target miR-148a to alleviate cartilage damage in post-traumatic osteoarthritis (PTOA).

Thirty-two female rats were randomly divided into four groups: Sham-operated group (Sham group, n = 8), treadmill running group (R group, n = 8), anterior cruciate ligament transection (ACLT) group (ACLT group, n = 8), and ACLT + treadmill running group (ACLT + R group, n = 8). Histological evaluation was performed to observe the pathological changes in the cartilage of the rat knee. Micro-CT was performed to detect the bone morphological changes in the subchondral bone. RT-qPCR and Western-Blot were performed to detect changes in mRNA and protein levels of metabolic and inflammatory factors as well as changes in the expression of lncRNA H19 and miR-148a in cartilage. The Flexcell 5000™ Tension System was used to further validate that lncRNA H19 has mechanosensitivity in vitro. Finally, cell transfection techniques were used to knock down the expression of lncRNA H19 in chondrocytes to validate the regulatory role of lncRNA H19/miR-148a in cartilage metabolism.

ACLT combined with treadmill running aggravated the abnormal hyperplasia of subchondral bone in the lateral tibial plateau of the rat knee joint, disturbed the balance of cartilage metabolism, induced cartilage inflammatory response and chondrocyte pyroptosis, which eventually led to cartilage damage and PTOA. Importantly, we found that the expression of lncRNA H19 was significantly downregulated in the cartilage of the ACLT + R group. Bioinformatics analysis revealed that miR-148a may be a direct target of lncRNA H19. Subsequently, we focused on the mechanosensitive of lncRNA H19. Subsequently, moderate-intensity mechanical tension stress reversed the expression of lncRNA H19 and autophagy-related factors in inflammatory chondrocytes, while miR-148a showed an opposite expression trend, demonstrating that mechanosensitive lncRNA H19 may be involved in regulating the chondrocyte inflammatory response by targeting miR-148a and activating autophagy. Cell transfection experiments revealed that lncRNA H19 knockdown upregulated miR-148a expression and significantly inhibited the autophagy level of chondrocytes without significant alteration of chondrocyte pyroptosis, which in turn exacerbated the inflammatory response of chondrocytes.

Mechanosensitive lncRNA H19 can promote chondrocyte autophagy rather than pyroptosis by targeting miR-148a, thus alleviating cartilage damage in PTOA. LncRNA H19 may be a potential therapeutic target for PTOA.

Emerging evidence highlights the involvement of long non-coding RNAs (lncRNAs) and ferroptosis in the pathogenesis of traumatic brain injury (TBI). However, the regulatory role of lncRNAs in TBI-induced ferroptosis remains poorly understood. This study aims to investigate the role of a specific lncRNA, noncoding transcript of chemokine (C-C motif) ligand 4 (Ccl4) overlapping (Ntoco), in the regulation of ferroptosis following TBI and explore its potential as a therapeutic target.

The expression levels of Ntoco following controlled cortical injury (CCI) in mice were measured using real-time PCR. Behavioral tests post-injury were assessed using the rotarod test and Morris water maze, and lesion volume was evaluated using micro-MRI. Ntoco binding proteins were identified using RNA pull-down and RNA immunoprecipitation. RNA sequencing was employed to identify Ntoco-related pathways. Western blotting and co-immunoprecipitation were used to measure protein levels and ubiquitination processes.

Ntoco upregulation was observed in CCI mice. Ntoco knockdown inhibited neuron ferroptosis, reduced lesion volume, and improved spatial memory following TBI. Ntoco overexpression promoted ferroptosis in neurons. Mechanistically, Ntoco facilitated K48-linked ubiquitination and degradation of proteins by binding to Hnrnpab, suppressing the NF-κB/Lcn2 signaling pathway. This included reduced phosphorylation of IkBα, increased phosphorylation of IKKα/β, nuclear translocation of the NF-κB p65 subunit, and elevated Lcn2 expression.

Our findings suggest that Ntoco plays a crucial role in TBI-induced ferroptosis by modulating the NF-κB/Lcn2 signaling pathway. Targeting Ntoco may provide a promising therapeutic strategy to mitigate ferroptosis and improve outcomes following TBI.

The optimisation of livestock production relies on efficient energy metabolism. This review focused on elaborate regulatory processes governed by non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). It explores the complex energy metabolism processes in livestock, elucidating the functions of ncRNAs in the expression of genes and pathways. miRNAs have been identified as significant regulators of glycolysis and glucose metabolism, whereas lncRNAs are known to affect adipogenesis and mitochondrial activity. Moreover, circRNAs have a substantial influence on the regulation of energy. In addition, this is not only enriching non-coding RNA-mediated energy control but also sheds light on possible applications. It is derived from its ability to condense complex molecular systems, thereby offering crucial insights to researchers. Through a comprehensive analysis of the intricate relationship between ncRNAs and energy metabolism, the information of this review provides a valuable framework for the implementation of focused interventions that hold the potential to significantly enhance the efficiency of livestock production.

Hematophagous female mosquitoes are important vectors of numerous devastating human diseases, posing a major public health threat. Effective prevention and control of mosquito-borne diseases rely considerably on progress in understanding the molecular mechanisms of various life activities, and accordingly, the molecules that regulate the various life activities of mosquitoes are potential targets for implementing future vector control strategies. Many long non-coding RNAs (lncRNAs) have been identified in mosquitoes and significant progress has been made in determining their functions. Here, we present a comprehensive overview of the research advances on mosquito lncRNAs, including their molecular identification, function, and interaction with other non-coding RNAs, as well as their synergistic regulatory roles in mosquito life activities. We also highlight the potential roles of competitive endogenous RNAs in mosquito growth and development, as well as in insecticide resistance and virus-host interactions. Insights into the biological functions and mechanisms of lncRNAs in mosquito life activities, viral replication, pathogenesis, and transmission will contribute to the development of novel drugs and safe vaccines.

Non-small cell lung cancer (NSCLC) has emerged as one of the most prevalent malignancies worldwide. N6-methyladenosine (m6A) methylation, a pervasive epigenetic modification in long noncoding RNAs (lncRNAs), plays a crucial role in NSCLC progression. Here, we report that m6A modification and the expression of the lncRNA stem cell inhibitory RNA transcript (SCIRT) was significantly upregulated in NSCLC tissues and cells. Functional analysis revealed that SCIRT enhanced NSCLC cell proliferation, migration, invasion, and epithelial‒mesenchymal transition. The m6A modification of SCIRT can be installed by METTL3, which enhanced the stability of this lncRNA. Notably, SCIRT overexpression in response to DNA double-strand breaks (DSBs) sensitized cells to camptothecin (CPT) and impairs DNA homologous recombination repair. SCIRT directly interacted with SFPQ in vitro and was primarily localized in the nucleus. Furthermore, ectopic SCIRT expression upregulated SFPQ and activated the PI3K/Akt pathway following CPT treatment, suggesting an unexpected role of SCIRT in facilitating SFPQ-mediated DSB repair. In brief, our findings highlight the oncogenic role of SCIRT in NSCLC by binding SFPQ and activating PI3K/Akt signaling, presenting a promising therapeutic target for personalized NSCLC treatment.

Vascular aging (VA) is a common etiology of various chronic diseases and represents a major public health concern. Intermittent hypoxia (IH) associated with obstructive sleep apnea-hypopnea syndrome (OSAHS) is a primary pathological and physiological driver of OSAHS-induced systemic complications. A substantial proportion of OSAHS patients, estimated to be between 40% and 80%, have comorbidities such as hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, aneurysm, and stroke, all of which are closely associated with VA. This review examines the molecular and cellular features common to both OSAHS and VA, highlighting decreased melatonin secretion, impaired autophagy, increased apoptosis, increased inflammation and pyroptosis, increased oxidative stress, accelerated telomere shortening, accelerated stem cell depletion, metabolic disorders, imbalanced protein homeostasis, epigenetic alterations, and dysregulated neurohormonal signaling. The accumulation and combination of these features may underlie the pathophysiological link between OSAHS and VA, but the exact mechanisms by which OSAHS affects VA may require further investigation. Taken together, these findings suggest that OSAHS may serve as a novel risk factor for VA and related vascular disorders, and that targeting these features may offer therapeutic potential to mitigate the vascular risks associated with OSAHS.

Grapes are considered a crucial fruit crop with extensive uses globally. Cluster compactness is an undesirable trait for the productivity of Yaghooti grape, and it reduces its desirability among consumers. The RNA-Seq data were analyzed in three stages of cluster development using the FEELnc software, leading to the identification of 849 lncRNAs. 183 lncRNAs were differentially expressed during cluster development stages. The GO and KEGG enrichment analyses of these lncRNAs revealed that they target 1,814 genes, including CKX, PG, PME, NPC2, and UGT. The analysis demonstrated a relationship between these lncRNAs and key processes such as grape growth and development, secondary metabolite synthesis, and resistance to both biotic and abiotic stresses. These findings, combined with molecular experiments on lncRNA interactions with other regulatory factors, could enhance Yaghooti grape quality and decrease cluster compactness.

The precise role of lncRNAs in skeletal muscle development and atrophy remain elusive. We conducted a bioinformatic analysis of 26 GEO datasets from mouse studies, encompassing embryonic development, postnatal growth, regeneration, cell proliferation, and differentiation, using R and relevant packages (limma et al.). LncRNA-miRNA relationships were predicted using miRcode and lncBaseV2, with miRNA-mRNA pairs identified via miRcode, miRDB, and Targetscan7. Based on the ceRNA theory, we constructed and visualized the lncRNA-miRNA-mRNA regulatory network using ggalluvial among other R packages. GO, Reactome, KEGG, and GSEA explored interactions in muscle development and regeneration. We identified five candidate lncRNAs (Xist, Gas5, Pvt1, Airn, and Meg3) as potential mediators in these processes and microgravity-induced muscle wasting. Additionally, we created a detailed lncRNA-miRNA-mRNA regulatory network, including interactions such as lncRNA Xist/miR-126/IRS1, lncRNA Xist/miR-486-5p/GAB2, lncRNA Pvt1/miR-148/RAB34, and lncRNA Gas5/miR-455-5p/SOCS3. Significant signaling pathway changes (PI3K/Akt, MAPK, NF-κB, cell cycle, AMPK, Hippo, and cAMP) were observed during muscle development, regeneration, and atrophy. Despite bioinformatics challenges, our research underscores the significant roles of lncRNAs in muscle protein synthesis, degradation, cell proliferation, differentiation, function, and metabolism under both normal and microgravity conditions. This study offers new insights into the molecular mechanisms governing skeletal muscle development and regeneration.

Functional RNA participates in various life processes in cells. However, there is currently a lack of effective methods to screen for functional RNA. Here, we developed a technology named random high-throughput screening (rHTS). rHTS uses a random library of ∼250-nt synthesized RNA fragments, with high uniformity and abundance. These fragments are circularized into circular RNA by an auto-cyclizing ribozyme to improve their stability. Using rHTS, we successfully screened and identified three RNA fragments contributing significantly to the growth of Escherichia coli, one of which possesses coding potential. Moreover, we found that two noncoding RNAs (ncRNAs) effectively inhibited the growth of E. coli, in vivo rather than in vitro. Subsequently, we applied the rHTS to a coenzyme-dependent screening platform. In this context, two ncRNAs were identified that could effectively promote the conversion from NADPH to NADP+. Exogenous expression of these two ncRNAs was able to increase the conversion rate of glycerol dehydrogenase from glycerol to 1,3-dihydroxyacetone from 18.3% to 21.8% and 23.2%, respectively. These results suggest that rHTS is a powerful technology for functional RNA mining.

It has been discovered that Trichorhinophalangeal Syndrome-1 (TRPS1), a novel member of the GATA transcription factor family, participates in both normal physiological processes and the development of numerous diseases. Recently, TRPS1 has been identified as a new biomarker to aid in cancer diagnosis and is very common in breast cancer (BC), especially in triple-negative breast cancer (TNBC). In this review, we discussed the structure and function of TRPS1 in various normal cells, focused on its role in tumorigenesis and tumor development, and summarize the research status of TRPS1 in the occurrence and development of BC. We also analyzed the potential use of TRPS1 in guiding clinically personalized precision treatment and the development of targeted drugs.

High-throughput sequencing technologies and innovative bioinformatics tools discovered that most of the genome is transcribed into RNA. However, only a fraction of the RNAs in cell translates into proteins, while the majority of them are categorized as noncoding RNAs (ncRNAs). The ncRNAs with more than 200 nt without protein-coding ability are termed long noncoding RNAs (lncRNAs). Hundreds of studies established that lncRNAs are a crucial RNA family regulating gene expression. Regulatory RNAs, including lncRNAs, modulate gene expression by interacting with RNA, DNA, and proteins. Several databases and computational tools have been developed to explore the functions of lncRNAs in cellular physiology. This chapter discusses the tools available for lncRNA functional analysis and provides a detailed workflow for the computational analysis of lncRNAs.

Epigenetics mechanisms play a significant role in human diseases by altering DNA methylation status, chromatin structure, and/or modifying histone proteins. By modulating the epigenetic status, the expression of genes can be regulated without any change in the DNA sequence itself. Epigenetic drugs exhibit promising therapeutic efficacy against several epigenetically originated diseases including several cancers, neurodegenerative diseases, metabolic disorders, cardiovascular disorders, and so forth. Currently, a considerable amount of research is focused on discovering new drug molecules to combat the existing research gap in epigenetic drug therapy. A novel and efficient delivery system can be established as a promising approach to overcome the drawbacks associated with the current epigenetic modulators. Therefore, formulating the existing epigenetic drugs with distinct encapsulation strategies in nanocarriers, including solid lipid nanoparticles, nanogels, bio-engineered nanocarriers, liposomes, surface modified nanoparticles, and polymer-drug conjugates have been examined for therapeutic efficacy. Nonetheless, several epigenetic modulators are untouched for their therapeutic potential through different delivery strategies. This review provides a comprehensive up to date discussion on the research findings of various epigenetics mechanism, epigenetic modulators, and delivery strategies utilized to improve their therapeutic outcome. Furthermore, this review also highlights the recently emerged CRISPR tool for epigenome editing.

Long-lasting persistence within infected cells is a major challenge for viral pathogens, as it necessitates an exact regulation of viral replication to reduce viral cytopathic effects. This is particularly challenging for viruses that persistently infect cells with limited renewal capabilities, such as neurons. Accordingly, neurotropic viruses have evolved various specific mechanisms to promote a long-lasting persistent infection in the host cells without inducing an exacerbated cytopathic effect. Borna disease virus (BDV) and Human immunodeficiency virus (HIV) are two neurotropic RNA viruses that, in contrast to other RNA viruses, can establish long-lasting intranuclear infections within the nervous system. These viruses interact with different cellular processes such as epigenetic modifications to develop a successful persistence infection. Studies show that cellular epigenetic mechanisms play a significant role in the pathogenesis of BDV and HIV and their neurological disorders. Hence, targeting these mechanisms by epigenetic modulator agents can be regarded as a novel therapeutic strategy to manage BDV- and HIV-associated neurological diseases. This review provides an overview of different epigenetic modulator compounds as a potential therapeutic target for controlling persistent neurotropic intranuclear infections caused by BDV and HIV.

Prostate cancer (PCa) is a major health concern that necessitates appropriate diagnostic approaches for timely intervention. This review critically evaluates the role of liquid biopsy techniques, focusing on blood- and urine-based biomarkers, in overcoming the limitations of conventional diagnostic methods. The 4Kscore test and Prostate Health Index have demonstrated efficacy in distinguishing PCa from benign conditions. Urinary biomarker tests such as PCa antigen 3, MyProstateScore, SelectMDx, and ExoDx Prostate IntelliScore test have revolutionized risk stratification and minimized unnecessary biopsies. Emerging biomarkers, including non-coding RNAs, circulating tumor DNA, and prostate-specific antigen (PSA) glycosylation, offer valuable insights into PCa biology, enabling personalized treatment strategies. Advancements in non-invasive liquid biomarkers for PCa diagnosis may facilitate the stratification of patients and avoid unnecessary biopsies, particularly when PSA is in the gray area of 4 to 10 ng/mL.

Long noncoding RNAs (lncRNAs) serve pivotal roles in cancer biology. The present study investigated the oncogenic roles of lncRNAs in renal cell carcinoma (RCC) and their potential as prognostic biomarkers. The lncRNA leucine‑rich repeat containing 75 A‑antisense RNA1 (LRRC75A‑AS1) was identified through lncRNA microarray as a potential lncRNA that may predict the efficacy of immune checkpoint inhibitor therapy and cancer progression in RCC. The present study subsequently assessed the expression of LRRC75A‑AS1 in 212 patients with clear cell RCC (ccRCC) who underwent nephrectomy, and performed in vitro functional analysis of LRRC75A‑AS1 in RCC cell lines. Additionally, the interactions between LRRC75A‑AS1, microRNA (miR)‑370‑5p and ADAMTS5 were explored. LRRC75A‑AS1 was revealed to be significantly upregulated in ccRCC tissues compared with in adjacent normal tissues, and high LRRC75A‑AS1 expression was associated with poor prognosis, including lower progression‑free survival, in patients with RCC. The knockdown of LRRC75A‑AS1 in RCC cell lines resulted in reduced cell proliferation and invasion, highlighting its role in promoting tumorigenesis. Furthermore, the interaction among LRRC75A‑AS1, miR‑370‑5p and ADAMTS5 was suggested as a regulatory mechanism underlying RCC progression. These findings indicated that LRRC75A‑AS1 may function as an oncogene in RCC, promoting cell proliferation and invasion. Its significant upregulation in ccRCC tissues and association with poor prognosis underscore its potential as a prognostic biomarker for RCC. Understanding the regulatory interactions among LRRC75A‑AS1, miR‑370‑5p and ADAMTS5 may provide new insights into the molecular mechanisms underlying RCC and facilitate the identification of novel therapeutic targets.

Long non-coding RNAs (lncRNAs) are a type of non-coding RNA molecules exceeding 200 nucleotides in length and that do not encode proteins. The dysregulated expression of lncRNAs has been identified in various diseases, holding therapeutic significance. Over the past decade, numerous computational resources have been published in the field of lncRNA. In this chapter, we have provided a comprehensive review of the databases as well as predictive tools, that is, lncRNA databases, machine learning based algorithms, and tools predicting lncRNAs utilizing different techniques. The chapter will focus on the importance of lncRNA resources developed for different organisms specifically for humans, mouse, plants, and other model organisms. We have enlisted important databases, primarily focusing on comprehensive information related to lncRNA registries, associations with diseases, differential expression, lncRNA transcriptome, target regulations, and all-in-one resources. Further, we have also included the updated version of lncRNA resources. Additionally, computational identification of lncRNAs using algorithms like Deep learning, Support Vector Machine (SVM), and Random Forest (RF) was also discussed. In conclusion, this comprehensive overview concludes by summarizing vital in silico resources, empowering biologists to choose the most suitable tools for their lncRNA research endeavors. This chapter serves as a valuable guide, emphasizing the significance of computational approaches in understanding lncRNAs and their implications in various biological contexts.

Acute myeloid leukemia (AML) is a rare tumor that invades the blood and bone marrow, it is rapidly progressive, highly aggressive, and difficult to cure. Studies have shown that long non-coding RNA (lncRNA) and ferroptosis play important roles in AML. However, few studies have been done on ferroptosis-related lncRNA for AML. To investigate the role of ferroptosis-related lncRNA in AML prognosis, we screened the differentially expressed genes related to ferroptosis and lncRNA. Ferroptosis-related lncRNA associated with AML prognosis was obtained by Pearson correlation analysis. By using univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox analysis, the ten prognostic genes were used for constructing the prognostic model. The model was then validated using a Kaplan-Meier analysis and Cox regression analysis. The ROC results have shown that the model could better predict AML survival. We identified some mutated genes that may affect the poor prognosis based on the somatic mutation analysis. The enrichment pathway analysis of prognostic genes revealed that these genes were mainly enriched in some immune pathways and cancer pathways. By immune infiltration analysis, we found that high-risk patients may respond better to immunotherapy.

The involvement of long non-coding RNAs (lncRNAs) in glioma carcinogenesis has gradually been identified. Herein, we aimed to explore the function and mechanism of lncRNA muskelin 1 antisense RNA (MKLN1-AS) in glioma cell oncogenic properties. Quantitative real-time polymerase chain reaction was utilized to test the expression of MKLN1-AS, miR-126-5p, and TEAD1 (TEA Domain Transcription Factor 1) mRNA expression. Oncogenic properties of glioma cells were characterized using 5-ethynyl-2'-deoxyuridine, flow cytometry, wound healing, transwell, and tube formation assays, respectively. Levels of TEAD1 protein, mobility-related proteins, and Hippo pathway-related proteins were examined by Western blotting. The binding between miR-126-5p and MKLN1-AS or TEAD1 was confirmed by using dual-luciferase reporter and pull-down assays. The murine xenograft model was established for in vivo analysis. Levels of MKLN1-AS in glioma tissues and cell lines were higher, functionally, MKLN1-AS deficiency could suppress glioma cell proliferation, migration, invasion, and angiogenesis, and induce apoptosis in vitro, as well as impede tumor growth in vivo. Mechanistically, miR-126-5p was targeted by MKLN1-AS, miR-126-5p directly targeted TEAD1. The suppressing effects of MKLN1-AS deficiency on glioma cell oncogenic properties were abolished by TEAD1 overexpression or miR-126-5p inhibition. Besides, MKLN1-AS/miR-126-5p mediates the activation of Hippo pathway by TEAD1. MKLN1-AS knockdown weakened glioma cell oncogenic phenotypes and growth via TEAD1-Hippo pathway through miR-126-5p, indicating a new therapeutic target for glioma molecular therapy.

To understand the transcriptomic profile of an individual cell in a multicellular organism, we must comprehend its surrounding environment and the cellular space where distinct molecular stimuli responses are located. Contradicting the initial perception that RNAs were nonfunctional and that only a few could act in chromatin remodeling, over the last few decades, research has revealed that they are multifaceted, versatile regulators of most cellular processes. Among the various RNAs, long non-coding RNAs (LncRNAs) regulate multiple biological processes and can even impact cell fate. In this sense, the subcellular localization of lncRNAs is the primary determinant of their functions. It affects their behavior by limiting their potential molecular partner and which process it can affect. The fine-tuned activity of lncRNAs is also tissue-specific and modulated by their cis and trans regulation. Hence, the spatial context of lncRNAs is crucial for understanding the regulatory networks by which they influence and are influenced. Therefore, predicting a lncRNA's correct location is not just a technical challenge but a critical step in understanding the biological meaning of its activity. Hence, examining these peculiarities is crucial to researching and discussing lncRNAs. In this review, we debate the spatial regulation of lncRNAs and their tissue-specific roles and regulatory mechanisms. We also briefly highlight how bioinformatic tools can aid research in the area.

Extracellular vesicles (EVs) are lipid bilayer nanoparticles released from all known cells and are involved in cell-to-cell communication via their molecular content. EVs have been found in all tissues and body fluids, carrying a variety of biomolecules, including DNA, RNA, proteins, metabolites, and lipids, offering insights into cellular and pathophysiological conditions. Despite the emergence of EVs and their molecular contents as important biological indicators, it remains difficult to explore EV-mediated biological processes due to their small size and heterogeneity and the technical challenges in characterizing their molecular content. EV-associated small RNAs, especially microRNAs, have been extensively studied. However, other less characterized RNAs, including protein-coding mRNAs, long noncoding RNAs, circular RNAs, and tRNAs, have also been found in EVs. Furthermore, the EV-associated proteins can be used to distinguish different types of EVs. The spectrum of EV-associated RNAs, as well as proteins, may be associated with different pathophysiological conditions. Therefore, the ability to comprehensively characterize EVs' molecular content is critical for understanding their biological function and potential applications in disease diagnosis. Here, we set out to provide an overview of EV-associated RNAs and proteins as well as approaches currently being used to characterize them.

Acute myeloid leukemia (AML) is the abnormal proliferation of immature myeloid blast cells in the bone marrow. Currently, there are no universally recognized biomarkers for the early diagnosis, prognosis and effective treatment of AML to improve the overall survival of patients. Recent studies, however, have demonstrated that long noncoding RNAs (lncRNAs) are promising targets for the early diagnosis, prognosis and treatment of AML. A critical review of available data would be important to identify study gaps and provide perspectives. In this review, we explored comprehensive information on the potential use of lncRNAs as targets for the diagnosis, prognosis, and treatment of AML. LncRNAs are nonprotein-coding RNAs that are approximately 200 nucleotides long and play important roles in the regulation, metabolism and differentiation of tissues. In addition, they play important roles in the diagnosis, prognosis and treatment of different cancers, including AML. LncRNAs play multifaceted roles as oncogenes or tumor suppressor genes. Recently, deregulated lncRNAs were identified as novel players in the development of AML, making them promising prognostic indicators. Given that lncRNAs could have potential diagnostic marker roles, the lack of sufficient evidence identifying specific lncRNAs expressed in specific cancers hampers the use of lncRNAs as diagnostic markers of AML. The complex roles of lncRNAs in the pathophysiology of AML require further scrutiny to identify specific lncRNAs. This review, despite the lack of sufficient literature, discusses the therapeutic, diagnostic and prognostic roles of lncRNAs in AML and provides future insights that will contribute to studies targeting lncRNAs in the diagnosis, treatment, and management of AML.

Infectious bursal disease virus (IBDV) causes immunosuppression and high mortality in young chickens. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are important regulators during viral infection. However, detailed the regulatory mechanisms of lncRNA-miRNA-mRNA have not yet been described in IBDV infection. Here, we analysed the role of lncRNA53557/gga-miR-3530-5p/STAT1 axis in very virulent IBDV (vvIBDV) infection. Evidently upregulated expression of lncRNA53557 was observed in bursa of Fabricius and DT40 cells. Meanwhile, overexpression of lncRNA53557 promoted STAT1 expression and inhibited vvIBDV replication and vice versa, indicating that the upregulation of lncRNA53557 was part of the host antiviral defence. The subcellular fractionation assay confirmed that lncRNA53557 can be localized in the cytoplasm. Further, dual-luciferase reporter, RNA pulldown, FISH and RT-qPCR assays revealed that lncRNA53557 were directly bound to gga-miR-3530-5p and had a negative regulatory relationship between them. Subsequent mechanistic analysis showed that lncRNA53557 acted as a competing endogenous RNA (ceRNA) of gga-miR-3530-5p to relieve the repressive effect of gga-miR-3530-5p on its target STAT1, as well as Mx1, OASL, and ISG15, thereby suppressing vvIBDV replication. The study reveals that a network of enriched lncRNAs and lncRNA-associated ceRNA is involved in the regulation of IBDV infection, offering new insight into the mechanisms underlying IBDV-host interaction.