Understanding the core principles of ovarian cancer has been significantly improved through the exploration of Ferroptosis, a type of cell death triggered by iron that leads to an increase in lipid peroxides. Current research has shed light on the critical functions of non-coding RNAs, such as circRNAs, lncRNAs, and miRNAs, in regulating ferroptosis in ovarian cancer. The aim of this paper is to comprehensively analyze how ncRNAs influence the development of ferroptosis in ovarian cancer cells. In-depth exploration is undertaken to understand the intricate ways in which ncRNAs regulate essential elements of ferroptosis, including iron management and lipid peroxidation levels. We also investigate their significant involvement in the progression of this type of cellular demise. It should be emphasized that ncRNAs can impact the synthesis of crucial proteins, such as GPX4, a key contributor to the cellular defense against oxidation, and ACSL4, involved in lipid formation. In addition, we examine the correlation between ncRNAs and well-known pathways associated with oxidative stress and cell death. The consequences of these discoveries are noteworthy, since focusing on particular ncRNAs could potentially render ovarian cancer cells more vulnerable to ferroptosis, effectively combating drug resistance problems. This discussion highlights the growing significance of ncRNAs in governing ferroptosis and their potential as useful biomarkers and treatment targets for ovarian cancer. We intend to promote additional research into the involvement of ncRNAs in controlling ferroptosis, based on current findings, with the ultimate goal of informing targeted therapeutic strategies and improving long-term treatment outcomes for individuals suffering from OC.

Long noncoding RNAs (lncRNAs) have been recognized as significant modulators of gene expression and are essential for various biological functions, even though they don't appear to have the ability to encode proteins. Originally considered dark matter, lncRNAs have been recognized as being dysregulated and contributing to the onset, progression, and resistance to treatment of acute myeloid leukemia (AML). AML is a prevalent type of leukemia characterized by the disruption of myeloid cell differentiation, leading to an increased number of immature myeloid progenitor cells. Currently, the need for novel biomarkers and treatment targets to enhance therapeutic alternatives has led to a focus on lncRNAs as possible indicators for prognostic, therapeutic, and diagnostic systems in various human cancers, including AML. Recent research has recognized a limited set of lncRNAs as possible prognostic biomarkers or diagnoses in AML. This review evaluates the key research that highlights the significance of lncRNAs in AML and discusses their roles and impacts on the disease. Furthermore, we intend to underscore the importance of lncRNAs as new and trustworthy markers for the diagnosis, prediction, drug resistance, and targets for treatment in AML.

Extrachromosomal DNA (ecDNA) amplifications are prevalent drivers of human cancers. We show that ecDNAs exhibit elevated structural variants leading to gene fusions that produce oncogene fusion transcripts. The long noncoding RNA (lncRNA) gene PVT1 is the most recurrent structural variant across cancer genomes, with PVT1-MYC fusions arising most frequently on ecDNA. PVT1 exon 1 is the predominant 5' partner fused to MYC or other oncogenes on the 3' end. Mechanistic studies demonstrate that PVT1 exon 1 confers enhanced RNA stability for fusion transcripts, which requires PVT1 exon 1 interaction with SRSF1 protein. Genetic rescue of MYC-addicted cancer models and isoform-specific single-cell RNA sequencing of tumors reveal that PVT1-MYC better supports MYC dependency and better activates MYC target genes in vivo . Thus, the mutagenic landscape of ecDNA contributes to genome instability and generates chimeric fusions of lncRNA and mRNA genes, selecting PVT1 5' region as a stabilizer of oncogene mRNAs.

The chromodomain helicase DNA binding protein 7 (CHD7) is a nucleosome repositioner implicated in multiple cellular processes, including neuronal differentiation. We identified CHD7 genome-wide binding sites that regulate neuronal differentiation in an otic stem cell line. We identified CHD7 enrichment at the Sox11 promoter and 3' untranslated region (UTR). Sox11 is a transcription factor essential for neuronal differentiation. CRISPRi of Sox11 promoter or 3'UTR displayed decreased neurite lengths and reduced neuronal marker expression TUBB3 expression. We showed that the Sox11 locus resides at TAD boundaries, and CTCF marks the 3'UTR. We propose that CHD7 modulates chromatin accessibility of the Sox11 promoter and CTCF-marked insulators in the 3'UTR to facilitate neuronal differentiation. CRISPRi of the insulator site alters 3D chromatin organization, affects gene expression and ultimately perturbs cellular processes. Our results implicate a general mechanism of CHD7 in facilitating neuronal differentiation and provide insight into CHD7 dysfunction in CHARGE syndrome, a congenital disorder associated with hearing loss.

C-terminal binding protein 1 divergent transcript (CTBP1-DT) is a novel long non-coding RNA (lncRNA) located on human chromosome 4p16.3. Numerous studies have shown that CTBP1-DT plays a critical regulatory role in various human malignancies and non-malignant diseases. In several cancers, the expression of CTBP1-DT is upregulated, closely associated with the risk of 12 types of cancer, and strongly correlated with the clinical pathological features and poor prognosis of 10 of these cancers. Mechanistically, CTBP1-DT is stimulated by the transcription factors ETV5 and Sp1, or methylated by YTHDC1. By competitively inhibiting 12 microRNAs, it activates 3 signaling pathways that influence malignant behaviors of tumor cells, including proliferation, apoptosis, cell cycle arrest, migration, invasion, immune evasion, and chemoresistance. Importantly, it also encodes the microprotein DNA damage up-regulated protein (DDUP), which mediates cisplatin resistance through sustained response to DNA damage signals. Furthermore, CTBP1-DT has been implicated in the progression of non-malignant diseases such as diabetes and related conditions, cardiovascular diseases, and osteoarthritis. This review summarizes the latest research on the RNA and protein functions of CTBP1-DT in human diseases, outlines various molecular regulatory networks centered around CTBP1-DT, and discusses the opportunities and challenges of its clinical applications.

Breast cancer (BC) is a malignant tumor that has the highest morbidity and mortality rates in the female population, and its high tendency to metastasize is the main cause of poor clinical prognosis. Long non-coding RNAs (lncRNAs) have been extensively documented to exhibit aberrant expression in various cancers and influence tumor progression via multiple molecular pathways. These lncRNAs not only modulate numerous aspects of gene expression in cancer cells, such as transcription, translation, and post-translational modifications, but also play a crucial role in the reprogramming of energy metabolism by regulating metabolic regulators, which is particularly significant in advanced BC. This review examines the characteristics and mechanisms of lncRNAs in regulating BC cells, both intracellularly (e.g., cell cycle, autophagy) and extracellularly (e.g., tumor microenvironment). Furthermore, we explore the potential of specific lncRNAs and their regulatory factors as molecular markers and therapeutic targets. Lastly, we summarize the application of lncRNAs in the treatment of advanced BC, aiming to offer novel personalized therapeutic options for patients.

The post-anal tail is a common physical feature of vertebrates including mammals. Although it exhibits rich phenotypic diversity, its development has been evolutionarily conserved as early as the embryonic period. Genes participating in embryonic tail morphogenesis have hitherto been widely explored on the basis of experimental discovery, whereas the associated cis-regulatory elements (CREs) have not yet been systematically investigated for vertebrate/mammalian tail development.

Here, utilizing high-throughput sequencing schemes pioneered in mice, we profiled the dynamic transcriptome and CREs marked by active histone modifications during embryonic tail morphogenesis. Temporal and spatial disparity analyses revealed the genes specific to tail development and their putative CREs, which facilitated the identification of novel molecular expression features and potential regulatory influence of non-coding loci including long non-coding RNA (lncRNA) genes and CREs. Moreover, these identified sets of multi-omics data supply genetic clues for understanding the regulatory effects of relevant signaling pathways (such as Fgf, Wnt) dominating embryonic tail morphogenesis.

Our work brings new insights and provides exploitable fundamental datasets for the elucidation of the complex genetic mechanisms responsible for the formation of the vertebrate/mammalian tail.

Breast cancer (BC) is the most prevalent malignancy among women, characterized by extensive heterogeneity stemming from molecular and genetic alterations. This review explores the intricate epigenetic landscape of BC, highlighting the significant role of epigenetic modifications-particularly DNA methylation, histone modifications, and the influence of non-coding RNAs-in the initiation, progression, and prognosis of the disease. Epigenetic alterations drive crucial processes, including gene expression regulation, cell differentiation, and tumor microenvironment interactions, contributing to tumorigenesis and metastatic potential. Notably, aberrations in DNA methylation patterns, including global hypomethylation and hypermethylation of CpG islands, have been associated with distinct BC subtypes, with implications for early detection and risk assessment. Furthermore, histone modifications, such as acetylation and methylation, affect cancer cell plasticity and aggressiveness by profoundly influencing chromatin dynamics and gene transcription. Finally, non-coding RNAs contribute by modulating epigenetic machinery and gene expression. Despite advances in our knowledge, clinical application of epigenetic therapies in BC is still challenging, often yielding limited efficacy when used alone. However, combining epi-drugs with established treatments shows promise for enhancing therapeutic outcomes. This review underscores the importance of integrating epigenetic insights into personalized BC treatment strategies, emphasizing the potential of epigenetic biomarkers for improving diagnosis, prognosis, and therapeutic response in affected patients.

Postinfectious, diarrhea-predominant, irritable bowel syndrome (PI-IBS-D) is difficult to treat owing to its unknown pathophysiology. Extracellular vesicles (EVs) derived from human colon tissue and long noncoding RNAs (lncRNAs), such as growth arrest-specific 5 (GAS5), may play key roles in the pathophysiology of PI-IBS-D. To determine whether altered colonic EV lncRNA signaling leads to gastrointestinal dysfunction and heightened visceral nociception in patients with PI-IBS-D via the GAS5/miR-23ab/NMDA NR2B axis, we conducted translational studies, including those on (a) the role of colonic EV lncRNAs in patients with PI-IBS-D, human colonoids, and PI-IBS-D tissues; (b) i.p. injection of colonic EVs from patients with PI-IBS-D into Rab27a/b-/- mice (P-EV mice) to investigate whether colonic EVs drive visceral hypersensitivity in vivo via the GAS5/miR-23ab/NMDA NR2B axis; and (c) treatment of mice with oligo-miR-23 precursors and anti-GAS5 Vivo-Morpholinos for GAS5/miR-23ab/NMDA NR2B axis mechanisms. Colonic EVs from patients with PI-IBS-D, but not from control participants, demonstrated reduced miR-23a/b expression caused by enhanced GAS5 expression, which drives increased NR2B expression. Intraperitoneal injection of anti-GAS5-Vivo-Morpholino into P-EV mice increased miR-23 levels and decreased NR2B expression and VMR to CD. EVs are internal messengers that alter gastrointestinal function and increase visceral nociception in patients with PI-IBS-D. Strategies to deliver EVs to modulate GAS5/miR-23ab/NMDA NR2B axis signaling may lead to new and innovative treatments for patients with PI-IBS-D.

Gliomas, a type of malignant tumor, are marked by a short survival period and an unfavorable prognosis. Disulfide stress, which arises from an overabundance of intracellular cystine, can initiate disulfidoptosis, an emerging form of cell death. The link between gliomas and disulfidoptosis has not been extensively explored. This study breaks new ground by investigating the correlation between glioma prognosis and lncRNAs associated with disulfidoptosis, with the aim of improving glioma treatment strategies.

We analyzed 10 long non-coding RNAs (lncRNAs) co-expressed with disulfidoptosis genes, retrieved clinical information and gene expression profiles from glioma and normal groups in the TCGA database, and developed a prognostic model for lncRNAs based on this data. The receiver operating characteristic curve (ROC) was used to evaluate and validate the model's reliability. Furthermore, the Kaplan-Meier survival curve was employed to assess the disparity in overall survival (OS) among patients with varying risk scores. We also examined the tumor microenvironment (TME), immune cell infiltration, immune-related functions, tumor mutational burden (TMB), and OncoPredict in samples with differing risk scores. To confirm the expression variations of genes associated with prognostic models in cell lines, quantitative polymerase chain reaction (qPCR) was employed.

Eleven long non-coding RNAs (lncRNAs) were identified for constructing prognostic models by analyzing lncRNAs associated with disulfidoptosis genes using Cox regression and LASSO regression analyses. The study's findings indicate that these 11 key lncRNAs serve as independent predictors of overall survival (OS) in glioma patients. Moreover, the frequency with which patients of varying risk scores opt for immune checkpoint blockade (ICB) therapy and chemotherapy not only differs but also their responses to these treatments are significantly distinct, suggesting that the risk score could be a predictive factor for treatment response.

This research sheds light on the characteristics of disulfidoptosis in glioma, revealing that patterns of disulfidoptosis in patients can be effectively assessed using a risk score. Consequently, the judicious application of this prognostic model can significantly inform clinical treatment strategies and precision medicine for glioma, potentially improving patient outcomes.

Predicting long non-coding RNA (lncRNA)-protein interactions is essential for understanding biological processes and discovering new therapeutic targets. In this study, we propose a novel model based on inter-view contrastive learning and miRNA fusion for lncRNA-protein interaction (LPI) prediction, called ICMF-LPI, which utilizes a heterogeneous information network to enhance LPI prediction. The model integrates miRNA as a mediator, constructing an lncRNA-miRNA-protein network, and employs metapath to extract diverse relationships from heterogeneous graphs. By fusing miRNA-related information and leveraging contrastive learning across inter-views, ICMF-LPI effectively captures potential interactions. Experimental results, including five-fold cross-validation, demonstrate the model's superior performance compared to several state-of-the-art methods, with significant improvements in the area under the receiver operating characteristic curve and the area under the precision-recall curve metrics. Notably, even when direct LPI connections are excluded, ICMF-LPI still achieves competitive predictive accuracy, performing comparably or better than some existing models. This demonstrates that the proposed model is effective in scenarios where direct interaction data are unavailable. This approach offers a promising direction for developing predictive models in bioinformatics, particularly in challenging conditions.

Small nucleolar RNA host gene 10 (SNHG10) is a newly recognized long non-coding RNA (lncRNA) with significant implications in cancer biology. Abnormal expression of SNHG10 has been observed in various solid tumors and hematological malignancies. Research conducted in vivo and in vitro has revealed that SNHG10 plays a pivotal role in numerous biological processes, including cell proliferation, apoptosis, invasion and migration, drug resistance, energy metabolism, immune evasion, as well as tumor growth and metastasis. SNHG10 regulates tumor development through several mechanisms, such as competing with microRNA (miRNA) for binding sites, modulating various signaling pathways, influencing transcriptional activity, and affecting epigenetic regulation. The diverse biological functions and intricate mechanisms of SNHG10 highlight its considerable clinical relevance, positioning it as a potential pan-cancer biomarker and therapeutic target. This review aims to summarize the role of SNHG10 in tumorigenesis and cancer progression, clarify the molecular mechanisms at play, and explore its clinical significance in cancer diagnosis and prognosis prediction, along with its therapeutic potential.

Inflammatory bowel disease (IBD) is closely associated with the development of colorectal cancer (CRC) due to the chronic inflammatory response. Macrophages play critical roles in regulating the microenvironment to facilitate tumor progression. Exosomes are key modulators for the communication between macrophages and tumor cells. The mechanism of macrophage-derived exosomes in IBD-related CRC development remains unclear.

The macrophages were isolated using fluorescence activating cell sorter (FACS). The RNA and protein expressions in exosomes and CRC cells were examined by quantitative real-time polymerase chain reaction and western blot assays, respectively. CRC cell development was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, BrdU staining, Transwell assay, and spheroid formation assay. The level of stemness was determined by detecting the proportion of leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5)-positive CRC cells and the expression of LGR5, CD133, and CD44. Molecular interaction experiments were done using luciferase reporter assay and RNA immunoprecipitation assay. Xenograft tumor model in vivo and immunohistochemistry were used to observe the pathological changes.

Macrophage-derived exosomes from IBD-related CRC tissues were enriched with nuclear paraspeckle assembly transcript 1 (NEAT1) and able to promote the progression and stemness of CRC both in vitro and in vivo. The exosomal NEAT1 could sponge miR-34a-5p, leading to the restoration of PEA15 expression in CRC cells and promoting the development of CRC. Inhibition of NEAT1 in exosomes could effectivity inhibit the tumor growth in the CRC xenograft model.

These findings provide novel insights into how macrophages affect CRC development and highlight exosomal NEAT1 as a therapeutic target for CRC treatment.

Endemic cretinism (EC) is one of the most severe iodine deficiency disorders, leading to typical symptoms such as neurodevelopmental impairments or mental deficits. In addition to environmental factors, the pathogenesis of its genetic contribution remains unclear. The study revealed the differential expression profiles of long non-coding RNA(lncRNA) and messenger RNA(mRNA) based on high-throughput RNA-seq. GO and KEGG analyses were used to annotate the function and pathway of differentially expressed (DE) mRNA and co-expressed mRNA. The protein-protein interaction(PPI) network was established. The expression levels of three lncRNAs and six mRNAs were validated by quantitative real-time PCR analysis (qRT-PCR) and subjected to correlation analysis. Compared to controls, a total of 864 lncRNAs and 393 mRNAs were differentially expressed. The PPI network had 149 nodes and 238 edges, and three key protein-coding genes were observed. Levels of LINC01220 and target mRNA IDO1 were statistically elevated in EC patients. Differentially expressed lncRNA may be a new potential player in EC. LINC01220 and IDO1 might interact with each other to participate in EC. The biological process of regulation of postsynaptic membrane potential and the Rap1 signaling pathway might exert a regulating role in the pathophysiological process of EC. Our findings could provide more theoretical and experimental evidence for investigating the pathophysiological mechanisms of EC.

Recently, the various regulative functions of long non-coding RNAs (LncRNAs) have been well determined. Recently, the vital role of LncRNAs as gene regulators has been identified in the immune system, especially in the inflammatory response. All cells of the immune system are governed by a complex and ever-changing gene expression program that is regulated through both transcriptional and post-transcriptional processes. LncRNAs regulate gene expression within the cell nucleus by influencing transcription or through post-transcriptional processes that affect the splicing, stability, or translation of messenger RNAs (mRNAs). Recent studies in immunology have revealed substantial alterations in the expression of lncRNAs during the activation of the innate immune system as well as the development, differentiation, and activation of T cells. These lncRNAs regulate key aspects of immune function, including the manufacturing of inflammatory molecules, cellular distinction, and cell movement. They do this by modulating protein-protein interactions or through base pairing with RNA and DNA. Here we review the current understanding of the mechanism of action of lncRNAs as novel immune-related regulators and their impact on physiological and pathological processes related to the immune system, including autoimmune diseases. We also highlight the emerging pattern of gene expression control in important research areas at the intersection between immunology and lncRNA biology.

Previously considered junk or non-functional, long non-coding RNAs (lncRNAs) have emerged over the past few decades as pivotal components in both physiological and pathological processes, including cancer. Neuroblastoma-associated transcript-1 (NBAT-1) was initially discovered a decade ago as a risk-associated tumor suppressor lncRNA in neuroblastoma (NB). Subsequent studies have consistently demonstrated that NBAT-1 serves as a dedicated tumor suppressor in many cancers. NBAT-1 is significantly downregulated in cancer, which is closely linked to higher histological grades, increased metastasis, and poor survival in cancer patients suggesting NBAT-1's potential as a prognostic biomarker. In this review, we delve into the current body of literature, elucidating the tumor-suppressive roles of NBAT-1 and the underlying regulatory mechanisms in the context of human malignancies. Additionally, we shed light on the mechanisms contributing to the diminished expression of NBAT-1 and its potential as both a prognostic biomarker and a promising therapeutic target in cancer.

Intergenic transcription, either failure to terminate at the transcription end site (TES), or transcription initiation at other intergenic regions, is present in cultured cells and enhanced in the presence of stressors such as viral infection. Such intergenic transcription has not been characterized in natural biological samples such as pre-implantation embryos which express more than 10,000 genes and undergo drastic changes in DNA methylation. Using Automatic Readthrough Transcription Detection (ARTDeco) and poly(A)-selected RNA-seq libraries from in vivo developed bovine oocytes and embryos, we found abundant intergenic transcripts that we termed as read-outs (transcribed from 5 to 15 kb after TES) and read-ins (transcribed 1 kb upstream of reference genes, extending up to 15 kb upstream). Read-throughs (continued transcription from TES of expressed reference genes, 4-15 kb in length), however, were much fewer. For example, the numbers of read-outs and read-ins ranged from 3084 to 6565 or 33.36% to 66.67% of expressed reference genes at different stages of embryo development. The less copious read-throughs were at an average of 10% and significantly correlated with reference gene expression (p < 0.05). Interestingly, intergenic transcription did not seem to be random because many intergenic transcripts (1504 read-outs, 1045 read-ins, and 1021 read-throughs) were associated with common reference genes across all stages of pre-implantation development. Their expression also seemed to be regulated by developmental stages because many were differentially expressed (log2 fold change ≥ 2, p < 0.05). Additionally, while gradual but un-patterned decreases in DNA methylation densities 10 kb both up- and downstream of the intergenic transcribed regions were observed, the correlation between intergenic transcription and DNA methylation was insignificant. Finally, transcription factor binding motifs and polyadenylation signals were found in 27.2% and 12.15% of intergenic transcripts, respectively, suggesting considerable novel transcription initiation and RNA processing. In summary, in vivo developed oocytes and pre-implantation embryos express large numbers of intergenic transcripts, which are not related to the overall DNA methylation profiles either up- or downstream.

Peripheral nerve injury (PNI) can result in severe disabilities, profoundly impacting patients' quality of life and potentially endangering their lives. Therefore, understanding the potential molecular mechanisms that facilitate the regeneration of damaged nerves is crucial. Evidence indicates that Schwann cells (SCs) play a pivotal role in repairing peripheral nerve injuries. Previous studies have shown that RNA, particularly non-coding RNA (ncRNA), plays a crucial role in nerve regeneration, including the proliferation and dedifferentiation of SCs. In this review, the individual roles of ncRNA in SCs and PNI are analyzed. This review not only enhances the understanding of ncRNA's role in nerve injury repair but also provides a significant theoretical foundation and inspiration for the development of new therapeutic strategies.

Biological ageing can be defined as a gradual loss of homeostasis across various aspects of molecular and cellular function1,2. Mammalian brains consist of thousands of cell types3, which may be differentially susceptible or resilient to ageing. Here we present a comprehensive single-cell RNA sequencing dataset containing roughly 1.2 million high-quality single-cell transcriptomes of brain cells from young adult and aged mice of both sexes, from regions spanning the forebrain, midbrain and hindbrain. High-resolution clustering of all cells results in 847 cell clusters and reveals at least 14 age-biased clusters that are mostly glial types. At the broader cell subclass and supertype levels, we find age-associated gene expression signatures and provide a list of 2,449 unique differentially expressed genes (age-DE genes) for many neuronal and non-neuronal cell types. Whereas most age-DE genes are unique to specific cell types, we observe common signatures with ageing across cell types, including a decrease in expression of genes related to neuronal structure and function in many neuron types, major astrocyte types and mature oligodendrocytes, and an increase in expression of genes related to immune function, antigen presentation, inflammation, and cell motility in immune cell types and some vascular cell types. Finally, we observe that some of the cell types that demonstrate the greatest sensitivity to ageing are concentrated around the third ventricle in the hypothalamus, including tanycytes, ependymal cells, and certain neuron types in the arcuate nucleus, dorsomedial nucleus and paraventricular nucleus that express genes canonically related to energy homeostasis. Many of these types demonstrate both a decrease in neuronal function and an increase in immune response. These findings suggest that the third ventricle in the hypothalamus may be a hub for ageing in the mouse brain. Overall, this study systematically delineates a dynamic landscape of cell-type-specific transcriptomic changes in the brain associated with normal ageing that will serve as a foundation for the investigation of functional changes in ageing and the interaction of ageing and disease.

Neurodegenerative diseases (ND) are complex diseases of still unknown etiology. Lately, long non-coding RNAs (lncRNAs) have become increasingly popular and implicated in several pathologies as they have several roles and appear to be involved in all biological processes such as cell signaling and cycle control as well as translation and transcription. MEG3 is one of these and acts by binding proteins or directly or competitively binding miRNAs. It has a crucial role in controlling cell death, inflammatory process, oxidative stress, endoplasmic reticulum stress, epithelial-mesenchymal transition and other processes. Recent reports showed that MEG3 is a major driving force of the necrosis phenomena in AD, causing the death of neurons, and its upregulation in cancer patients was linked to tumor suppression. Dysregulation of MEG3 affects neuronal cell death, inflammatory process, smooth muscle cell proliferation and consequently leads to the initiation or the acceleration of the disease. This review examines the current state of knowledge concerning the level of expression and the regulatory function of MEG3 in relation to several NDs. In addition, we examined the relation of MEG3 with neurotrophic factors such as Tumor growth factor β (TGFβ) and its possible mechanism of action. A comprehensive and in-depth analysis of the role of MEG3 in ND could give a clearer picture about the initiation of the process of neuronal death and help develop an alternative therapy that targets MEG3.

Non-coding RNAs (ncRNAs) are RNA molecules that are transcribed from DNA but are not translated into proteins. Studies over the past decades have revealed that ncRNAs can be classified into small RNAs, long non-coding RNAs and circular RNAs by genomic size and structure. Accumulated evidences have eludicated the critical roles of these non-coding transcripts in regulating gene expression through transcription and translation, thereby shaping cellular function and disease pathogenesis. Notably, recent studies have investigated the function of ncRNAs as competitive endogenous RNAs (ceRNAs) that sequester miRNAs and modulate mRNAs expression. The ceRNAs network emerges as a pivotal regulatory function, with significant implications in various diseases such as cancer and neurodegenerative disease. Therefore, we highlighted multiple bioinformatics tools and databases that aim to predict ceRNAs interaction. Furthermore, we discussed limitations of using current technologies and potential improvement for ceRNAs network detection. Understanding of the dynamic interplay within ceRNAs may advance the biological comprehension, as well as providing potential targets for therapeutic intervention.

The pathophysiology of obstructive sleep apnea (OSA) and diabetes mellitus (DM) is still unknown, despite clinical reports linking the two conditions. After investigating potential roles for DM-related genes in the pathophysiology of OSA, our goal is to investigate the molecular significance of the condition. Machine learning is a useful approach to understanding complex gene expression data to find biomarkers for the diagnosis of OSA.

Differentially expressed analysis for OSA and DM data sets obtained from GEO were carried out firstly. Then four machine algorithms were used to screen candidate biomarkers. The diagnostic model was constructed based on key genes, and the accuracy was verified by ROC curve, calibration curve and decision curve. Finally, the CIBERSORT algorithm was used to explore immune cell infiltration in OSA.

There were 32 important genes that were considered to be related both in OSA and DM datasets by differentially expressed analysis. Through enrichment analysis, the majority of these genes are enriched in immunological regulation, oxidative stress response, and nervous system control. When consensus characteristics from all four approaches were used to predict OSA diagnosis, STK17A was thought to have a high degree of accuracy. In addition, the diagnostic model demonstrated strong performance and predictive value. Finally, we explored the immune cells signatures of OSA, and STK17A was strongly linked to invasive immune cells.

STK17A has been discovered as a gene that can differentiate between individuals with OSA and DM based on four machine learning methods. In addition to offering possible treatment targets for DM-induced OSA, this diagnostic approach can identify high-risk DM patients who also have OSA.

Biological processes intricately intertwine with tumorigenesis, significantly influencing treatment outcomes and prognosis. However, the mechanisms fostering mucoepidermoid carcinoma (MEC) remain inadequately elucidated. This research utilizes expression profiles of lncRNAs from clinical MEC tissues and matched normal glandular tissues, integrating public data to explore the biological mechanisms and immune microenvironment characteristics of tumorigenesis. Gene set enrichment analysis identified key pathways, and a customized epithelial-mesenchymal transition (EMT) score elucidated the relationship between pathological processes and prognosis, while an immune signature revealed tumor microenvironment characteristics. MECs exhibited significant enrichment in EMT pathway, with key genes such as Secretogranin II, tissue factor pathway inhibitor 2, and periostin identified as contributors to the EMT process. High EMT scores correlated with upregulated EMT and immune response activity, indicating poor prognosis. Single-sample gene set enrichment analysis unveiled the tumors' immune infiltration signature, suggesting active antigen presentation and a positive immune response for immunotherapy. Additionally, SLC2A1-AS1 and CERS6-AS1 were identified as potential mediators of EMT and the immune environment. This study provides insights into the biological processes of MEC tumorigenesis and identifies potential therapeutic targets for future research.

MiRNAs represent a non-coding RNA class that regulate gene expression and pathways. While miRNAs are evolutionary conserved most data stems from Homo sapiens and Mus musculus. As miRNA expression is highly tissue specific, we developed miRNATissueAtlas to comprehensively explore this landscape in H. sapiens. We expanded the H. sapiens tissue repertoire and included M. musculus. In past years, the number of public miRNA expression datasets has grown substantially. Our previous releases of the miRNATissueAtlas represent a great framework for a uniformly pre-processed and label-harmonized resource containing information on these datasets. We incorporate the respective data in the newest release, miRNATissueAtlas 2025, which contains expressions from 9 classes of ncRNA from 799 billion reads across 61 593 samples for H. sapiens and M. musculus. The number of organs and tissues has increased from 28 and 54 to 74 and 373, respectively. This number includes physiological tissues, cell lines and extracellular vesicles. New tissue specificity index calculations build atop the knowledge of previous iterations. Calculations from cell lines enable comparison with physiological tissues, providing a valuable resource for translational research. Finally, between H. sapiens and M. musculus, 35 organs overlap, allowing cross-species comparisons. The updated miRNATissueAtlas 2025 is available at https://www.ccb.uni-saarland.de/tissueatlas2025.

Long non-coding RNAs (lncRNAs) are critical regulators of physiological and pathological processes, with their dysregulation increasingly implicated in aging and Alzheimer's disease (AD). Using spatial transcriptomics, we analyzed 78 postmortem brain sections from 21 ROSMAP participants to map the spatial expression of lncRNAs in the dorsolateral prefrontal cortex of aged human brains. Compared to mRNAs, lncRNAs exhibited greater subregion-specific expression, with enrichment in antisense and lincRNA biotypes. Network analysis identified 193 gene modules across eight subregions, including lncRNA-enriched modules involved in critical biological processes. We also identified AD differentially expressed (DE) lncRNAs, which showed greater subregion specificity than AD DE mRNAs. Gene set enrichment analysis highlighted the involvement of these AD DE lncRNAs in epigenetic regulation and chromatin remodeling, including enrichment for HDAC target genes such as OIP5-AS1. Statistical modeling suggested that interactions between OIP5-AS1 and HDAC proteins, particularly HDAC11, were associated with tau tangles in excitatory neurons and plaque burden in microglia. This study provides a comprehensive resource of lncRNA spatial expression in the aged human brain and uncovers potential functional roles of lncRNAs in AD pathogenesis.

Single-cell omics technologies have revolutionized the study of long non-coding RNAs (lncRNAs), offering unprecedented resolution in elucidating their expression dynamics, cell-type specificity, and associated gene regulatory networks (GRNs). Concurrently, the integration of artificial intelligence (AI) methodologies has significantly advanced our understanding of lncRNA functions and its implications in disease pathogenesis. This chapter discusses the progress in single-cell omics data analysis, emphasizing its pivotal role in unraveling the molecular mechanisms underlying cellular heterogeneity and the associated regulatory networks involving lncRNAs. Additionally, we provide a summary of single-cell omics resources and AI models for constructing single-cell gene regulatory networks (scGRNs). Finally, we explore the challenges and prospects of exploring scGRNs in the context of lncRNA biology.

Long intergenic noncoding RNAs (lincRNAs) have a variety of properties that differ from those of messenger RNAs (mRNAs) encoding proteins. Long intergenic nonprotein coding RNA 667 (LINC00667) is a non-coding transcript located on chromosome 18p11.31. Recently, many studies have found that LINC00667 can enhance the progression of various cancers and play a key part in a lot of diseases, such as tumorigenesis. Therefore, LINC00667 can be recognized as a potential biomarker and therapeutic target. So, we reviewed the biological functions, relevant mechanisms, as well as clinical significance of LINC00667 in several human cancers in detail.

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.

Life expectancy in cancer patients has been extended in recent years, thanks to major breakthroughs in therapeutic developments. However, this also unmasked an increased incidence of cardiovascular diseases in cancer survivors, which is in part attributable to cancer therapy-related cardiovascular toxicity. Non-coding RNAs (ncRNAs) have received much appreciation due to their impact on gene expression. NcRNAs, which include microRNAs, long ncRNAs and circular RNAs, are non-protein-coding transcripts that are involved in the regulation of various biological processes, hence shaping cell identity and behaviour. They have also been implicated in disease development, including cardiovascular diseases, cancer and, more recently, cancer therapy-associated cardiotoxicity. This review outlines key features of cancer therapy-associated cardiotoxicity, what is known about the roles of ncRNAs in these processes and how ncRNAs could be exploited as therapeutic targets for cardioprotection. LINKED ARTICLES: This article is part of a themed issue Non-coding RNA Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.2/issuetoc.

Hematological malignancies are typically treated with chemotherapy and radiotherapy as the first-line conventional therapies. However, non-coding RNAs (ncRNAs) are a rapidly expanding field of study in cancer biology that influences the growth, differentiation, and proliferation of tumors by targeting immunological checkpoints. This study reviews the results of studies (from 2012 to 2024) that consider the immune checkpoints and ncRNAs in relation to hematological malignancies receiving immunotherapy. This article provides a summary of the latest advancements in immunotherapy for treating hematological malignancies, focusing on the role of immune checkpoints and ncRNAs in the immune response and their capacity for innovative strategies. The paper also discusses the function of immune checkpoints in maintaining immune homeostasis and how their dysregulation can contribute to developing leukemia and lymphoma. Finally, this research concludes with a discussion on the obstacles and future directions in this rapidly evolving field, emphasizing the need for continued research to fully harness the capacity of immune checkpoints and ncRNAs in immunotherapy for hematological malignancies.

The establishment and maintenance of spermatogenesis is a complex process involving a vast of regulatory pathways. There is growing evidence revealing that long noncoding RNAs (lncRNA) play important roles in regulating testicular development and spermatogenesis in a stage-specific way. However, our understanding of how lncRNA regulates testicular development and spermatogenesis in black goats is quite limited. In the current study, we screened the transcriptomes (lncRNA and mRNA) of testicular from Guangxi black goats before puberty (3 days old, D3; 30 days old, D30), puberty (90 days old, D90) and postpuberty (180 days old, D180), in order to identify the lncRNA interaction with mRNAs contributes to goat spermatogenesis. The RNA-sequencing (RNA-seq) analysis showed that there were 1211, 12,180, 834 differential lncRNAs and 1196, 8838,269 differential mRNAs at the ages of D30 vs. D3, D90 vs. D30, and D180 vs. D90. The lncRNAs showed the most significantly changes from D30 to D90, which indicated that D90 was a key node of lncRNAs participated in the regulation of testicular development and spermatogenesis in black goat. According to functional enrichment analysis of GO and KEGG, we found that differentially expressed lncRNAs (DE lncRNAs) and their target genes regulated spermatogenesis through signal pathways including MAPK, Ras, and PI3K-Akt. Using cis- and trans-acting, 39 DE lncRNAs-targeted genes were found to be enriched for male reproduction. Of these, LOC108635509, which specific expressed in testis and upregulated the expression levels at D90, was found participated in the regulation of testicular development through promoting the proliferation of Sertoli cells (SCs). Overall, this study provides new insight into the regulatory mechanisms that support spermatogenesis and testicular development in black goats.

Gastrointestinal (GI) cancers, such as gastric cancer, hepatocellular carcinoma, colorectal cancer, and esophageal cancer, pose a significant medical and economic burden globally, accounting for the majority of new cancer cases and deaths each year. A lack of knowledge about the molecular mechanisms of GI cancers is reflected in the low efficacy of treatment for individuals with late stage and recurring illness. Understanding the molecular pathways that promote the growth of GI cancers may open doors for their therapy. Numerous long non-coding RNAs (lncRNAs) that are produced differently in normal and malignant tissues have been discovered by genome-wide techniques. The role of lncRNAs in the diagnosis, proliferation, metastasis, and drug resistance of different GI cancers has been investigated in recent research. LncRNAs may affect transcription, epigenetic modifications, protein/RNA stability, translation, and post-translational modifications via their interactions with DNA, RNAs, and proteins. Also, by functioning as competing endogenous RNAs (ceRNAs), they control the synthesis of certain microRNAs (miRNAs), which in turn modify the downstream target molecules of these miRNAs. Based on recent studies, lncRNAs in particular, CRNDE and HOTAIR, sponge different miRNAs and their downstream genes, which in turn regulate GI cancers development, including cell proliferation, invasion, migration, and chemoresistance. In this comprehensive review, we present an overview of the biological roles of CRNDE and HOTAIR and their associated mechanisms, miRNAs/mRNA pathways, in various GI cancers, encompassing colorectal cancer, hepatocellular carcinoma, esophageal cancer, and gastric cancer.

Emotional experiences often evoke neural plasticity that supports adaptive changes in behavior, including maladaptive plasticity associated with mood and substance use disorders. These adaptations are supported in part by experience-dependent activation of immediate-early response genes, such as Npas4 (neuronal PAS domain protein 4). Here we show that a conserved long noncoding enhancer RNA (lnc-eRNA), transcribed from an activity-sensitive enhancer, produces DNA:RNA hybrid R-loop structures that support three-dimensional chromatin looping between enhancer and proximal promoter and rapid Npas4 gene induction. Furthermore, in mouse models, Npas4 lnc-eRNA and its R-loop are required for the development of behavioral adaptations produced by chronic psychosocial stress or cocaine exposure, revealing a potential role for this regulatory mechanism in the transmission of emotional experiences.

Glioblastoma is the most common primary malignant brain tumour. Despite decades of intensive research in the disease, its prognosis remains poor, with an average survival of only 14 months after diagnosis. The remarkable level of intra- and interpatient heterogeneity is certainly contributing to the lack of progress in tackling this tumour. Epigenetic dysregulation plays an important role in glioblastoma biology and significantly contributes to intratumour heterogeneity. However, it is becoming increasingly clear that it also contributes to intertumour heterogeneity, which historically had mainly been linked to diverse genetic events occurring in different patients. In this review, we explore how DNA methylation, chromatin remodelling, microRNA (miRNA) dysregulation, and long noncoding RNA (lncRNA) alterations contribute to intertumour heterogeneity in glioblastoma, including its implications for advanced tumour stratification, which is the essential first step for developing more effective patient-specific therapeutic approaches.

Progress in the identification of core multi-protein modules within JAK/STAT pathway has enabled researchers to develop a better understanding of the linchpin role of deregulated signaling cascade in carcinogenesis and metastasis. More excitingly, complex interplay between JAK/STAT pathway and non-coding RNAs has been shown to reprogramme the outcome of signaling cascade and modulate immunological responses within tumor microenvironment. Wealth of information has comprehensively illustrated that most of this complexity regulates the re-shaping of the immunological responses. Increasingly sophisticated mechanistic insights have illuminated fundamental role of STAT-signaling in polarization of macrophages to M2 phenotype that promotes disease aggressiveness. Overall, JAK/STAT signaling drives different stages of cancer ranging from cancer metastasis to the reshaping of the tumor microenvironment. JAK/STAT signaling has also been found to play role in the regulation of infiltration and activity of natural killer cells and CD4/CD8 cells by PD-L1/PD-1 signaling. In this review, we have attempted to set spotlight on regulation of JAK/STAT pathway by microRNAs, long non-coding RNAs and circular RNAs in primary tumors and metastasizing tumors. Therefore, existing knowledge gaps need to be addressed to propel this fledgling field of research to the forefront and bring lncRNAs and circRNAs to the frontline of clinical practice. Leveraging the growing momentum will enable interdisciplinary researchers to gain transition from segmented view to a fairly detailed conceptual continuum.

Liver disease has emerged as a significant health concern, characterized by high rates of morbidity and mortality. Circulating exosomes have garnered attention as important mediators of intercellular communication, harboring protein and stable mRNAs, microRNAs, and long non-coding RNAs (lncRNA). This review highlights the involvement of exosomal lncRNA in the pathogenesis and diagnosis of various liver diseases. Notably, exosomal lncRNAs exhibit therapeutic potential as targets for conditions including hepatic carcinoma, hepatic fibrosis, and hepatic viral infections.

An online screening process was employed to identify studies investigating the association between exosomal lncRNA and various liver diseases.

Our study revealed a diverse array of lncRNAs carried by exosomes, including H19, Linc-ROR, VLDLR, MALAT1, DANCR, HEIH, ENSG00000248932.1, ENST00000457302.2, ZSCAN16-AS1, and others, exhibiting varied levels across different liver diseases compared to normal liver tissue. These exosomal-derived lncRNAs are increasingly recognized as pivotal biomarkers for diagnosing and prognosticating liver diseases, supported by emerging evidence. However, the precise mechanisms underlying the involvement of certain exosomal lncRNAs remain incompletely understood. Furthermore, the combined analysis of serum exosomes using ENSG00000258332.1, LINC00635, and serum AFP may serve as novel and valuable biomarker for HCC. Clinically, exosomal ATB expression is upregulated in HCC, while exosomal HEIH and RP11-513I15.6 have shown potential for distinguishing HCC related to HCV infection.

The lack of reliable biomarkers for liver diseases, coupled with the high specificity and sensitivity of exosomal lncRNA and its non-invasive detection, promotes exploring their role in pathogenesis and biomarker for diagnosis, prognosis, and response to treatment liver diseases.

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of cancer pathogenesis, influencing various cellular processes and contributing to tumorigenesis. Sphingolipid metabolism has garnered interest as a potential target for cancer therapy owing to its considerable diagnostic and prognostic value. Recent studies have demonstrated that lncRNAs regulate tumor-associated metabolic reprogramming via sphingolipid metabolism. However, the precise nature of the interactions between lncRNAs and sphingolipid metabolism remains unclear. This review summarizes the key roles of lncRNAs and sphingolipid metabolism in tumorigenesis. We emphasize that the interaction between lncRNAs and sphingolipid metabolism influences their impact on both cancer prognosis and drug resistance. These findings suggest that lncRNA-sphingolipid metabolism interaction holds great potential as a newl target for cancer treatment.

The mostly aggressive and extremely malignant type of central nervous system is Glioblastoma (GBM), which is characterized by an extremely short average survival time of lesser than 16 months. The primary cause of this phenomenon can be attributed to the extensively altered genome of GBM, which is characterized by the dysregulation of numerous critical signaling pathways and epigenetics regulations associated with proliferation, cellular growth, survival, and apoptosis. In light of this, different genetic alterations in critical signaling pathways and various epigenetics regulation mechanisms are associated with GBM and identified as distinguishing markers. Such GBM prognostic alterations are identified in PI3K/AKT, p53, RTK, RAS, RB, STAT3 and ZIP4 signaling pathways, metabolic pathway (IDH1/2), as well as alterations in epigenetic regulation genes (MGMT, CDKN2A-p16INK4aCDKN2B-p15INK4b). The exploration of innovative diagnostic and therapeutic approaches that specifically target these pathways is utmost importance to enhance the future medication for GBM. This study provides a comprehensive overview of dysregulated epigenetic mechanisms and signaling pathways due to mutations, methylation, and copy number alterations of in critical genes in GBM with prevalence and emphasizing their significance.

Most of the genome is transcribed into RNA but only 2% of the sequence codes for proteins. Non-coding RNA transcripts include a very large number of long noncoding RNAs (lncRNAs). A growing number of identified lncRNAs operate in cellular stress responses, for example in response to hypoxia, genotoxic stress, and oxidative stress. Additionally, lncRNA plays important roles in epigenetic mechanisms operating at chromatin and in maintaining chromatin architecture. Here, we address three lncRNA topics that have had significant recent advances. The first is an emerging role for many lncRNAs in cellular stress responses. The second is the development of high throughput screening assays to develop causal relationships between lncRNAs across the genome with cellular functions. Finally, we turn to recent advances in understanding the role of lncRNAs in regulating chromatin architecture and epigenetics, advances that build on some of the earliest work linking RNA to chromatin architecture.

Lung metastasis has garnered significant attention due to its prevalent occurrence. Pre-metastatic niche (PMN) establishment is a critical prerequisite for the onset of lung metastasis. Emerging evidence indicates that long noncoding RNAs (lncRNAs) play pivotal roles in the metastatic cascade to the lungs. However, the relationship between lncRNA expression profiles and the formation of PMN remains uncharacterized. This study aims to explore the expression profiles and potential roles of lncRNAs in the context of pre-metastatic lung microenvironment.

RNA sequencing was utilized to elucidate the lncRNA landscape in pre-metastatic lung of murine models. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to infer the prospective functions of the differentially expressed lncRNAs. Among these, lncRNA Gm5144-202 in alveolar macrophages (AMs) was further scrutinized for its role in driving M2 macrophage polarization, facilitating the formation of PMN, and orchestrating the apoptosis, proliferation, and migration of tumor cells in vitro.

A total of 232 lncRNAs exhibited differential expression in pre-metastatic murine lungs compared to normal controls, predominantly enriching pathways such as PI3K-Akt signaling, calcium signaling, neuroactive ligand-receptor interaction, and NF-κB signaling. Notably, lncRNA Gm5144-202 exhibited the most pronounced difference, with elevated level in alveolar macrophages (AMs) during the pre-metastatic phase. Silencing of lncRNA Gm5144-202 impeded the polarization of M2-like macrophages, suppressed the expression of factors critical for the formation of the PMN, and inhibited tumor cell invasion.

Our research delineated the lncRNA expression profiles in pre-metastatic pulmonary tissues and identified, for the first time, the pivotal role of lncRNA Gm5144-202 in modulating M2 macrophage polarization and tumor cell invasiveness. Consequently, targeting lncRNA Gm5144-202 holds substantial promise for translational applications aimed at mitigating pulmonary metastasis.

Obesity has escalated into a critical global health crisis, tripling in prevalence since the mid-1970s. This increase mirrors the rise in metabolic-associated diseases such as type 2 diabetes (T2D) and its complications, certain cancers, and cardiovascular conditions. While substantial research efforts have enriched our understanding and led to the development of innovative management strategies for these diseases, the suboptimal response rates of existing therapies remain a major obstacle to effectively managing obesity and its associated conditions. Over the years, inter-organ communication (IOC) has emerged as a crucial factor in the development and progression of metabolic disorders. Exosomes, which are nano-sized vesicular couriers released by cells, play a significant role in this communication by transporting proteins, lipids, and nucleic acids across cellular landscapes. The available evidence indicates that exosomal RNAs present in biofluids such as blood, urine, milk, vitreous humor (VH), and cerebrospinal fluid (CSF) are altered in numerous diseases, suggesting their diagnostic and therapeutic potential. Long non-coding RNAs contained in exosomes (exo-lncRNAs) have attracted considerable interest, owing to their ability to interact with critical components involved in a multitude of metabolic pathways. Recent studies have found that alterations in exo-lncRNAs in biofluids correlate with several metabolic parameters in patients with metabolic-associated conditions; however, their exact roles remain largely unclear. This review highlights the diagnostic and therapeutic potential of exosomal lncRNAs in obesity and its associated conditions, emphasizing their role in IOC and disease progression, aiming to pave the way for further research in this promising domain.

Since the introduction of the central dogma of molecular biology in 1958, various RNA species have been discovered. Messenger RNAs transmit genetic instructions from DNA to make proteins, a process facilitated by housekeeping non-coding RNAs (ncRNAs) such as small nuclear RNAs (snRNAs), ribosomal RNAs (rRNAs), and transfer RNAs (tRNAs). Over the past four decades, a wide array of regulatory ncRNAs have emerged as crucial players in gene regulation. In celebration of Cell's 50th anniversary, this Review explores our current understanding of the most extensively studied regulatory ncRNAs-small RNAs and long non-coding RNAs (lncRNAs)-which have profoundly shaped the field of RNA biology and beyond. While small RNA pathways have been well documented with clearly defined mechanisms, lncRNAs exhibit a greater diversity of mechanisms, many of which remain unknown. This Review covers pivotal events in their discovery, biogenesis pathways, evolutionary traits, action mechanisms, functions, and crosstalks among ncRNAs. We also highlight their roles in pathophysiological contexts and propose future research directions to decipher the unknowns of lncRNAs by leveraging lessons from small RNAs.