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.

Obesity is a significant public health concern directly associated with adipogenesis. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of adipogenesis. However, the roles of sex-specific lncRNAs in adipose tissue are not well comprehended. In this study, we used lncRNA microarrays to profile lncRNAs expression in visceral adipose tissues from obese and lean individuals, identifying LINC00278 as significantly and exclusively expressed in males. Elevated levels of LINC00278 were associated with higher body mass index (BMI) and non-remission after bariatric surgery in individuals with obesity. Mechanistic studies further revealed that METTL14 regulates the m6A methylation of LINC00278, which in turn binds with BRG1, activating the PPAR-γ2 pathway and promoting adipogenesis. Additionally, adipose-specific LINC00278 knock-in in C57BL/6 J mice resulted in adipocyte enlargement, increased body weight, higher body fat percentage, and impaired glucose metabolism. Treatment with the BRG1 inhibitor, BRM/BRG1 ATP Inhibitor-1, significantly alleviated the obesity phenotype in these mice. Our findings highlight the critical role of LINC00278 in male adipogenesis, suggesting that targeting the LINC00278-BRG1 axis could be a potential therapeutic strategy for managing obesity and related metabolic disorders in males.

Cancer has high mortality rate and occupies second position among major diseases. Despite extensive research and therapies, in every nook and corner of the world, death rate is increasing exponentially. Hallmarks of cancer are benchmarks of cancer cells describing the fundamental principle and capabilities of the cells transforming from normal to malignant tumour. One of the major ones among them is the deregulation of cellular metabolism or metabolic reprogramming, involving alterations in glucose and lipid metabolism. Progressive research in this area has visualized the vital role of lncRNAs in lipid metabolism with respect to AML. lncRNAs involve in various cellular processes and also contribute for significant functions of the cell like chromatin remodelling, transcriptional activation and repression, gene regulation, immune response, cell differentiation, and cell cycle regulation, in addition to oncogenic processes such as proliferation, angiogenesis, migration, and apoptosis. Structural similarities are observed among mRNAs and lncRNAs in terms of poly A-tail and 5' cap however protein-coding regions are lacking. A large body of evidence has shown that lncRNAs directly or indirectly mediate lipid metabolism by activating downstream genes. Considering their potential involvement in leukemia, these lncRNAs can be explored and considered as biomarkers for therapeutics, prognosis, and diagnosis. The present review is planned to summarize the functional classification of lncRNAs, the role of lipid metabolism in cancer, different lncRNAs involved in leukemia, and different cancer types related to lipid metabolism.

Long noncoding RNAs (lncRNAs) have been recently recognized as critical components of cancer biology linked to oncogenic processes. Certain lncRNAs are known to act as oncogenes, and the disease-specific expression of many lncRNAs makes them informative biomarkers. We identified 22 uncharacterized lncRNAs from RNA-seq data of 169 glioblastoma (GBM) tumor samples sequenced by The Cancer Genome Atlas (TCGA) consortium and studied their expression in TCGA diffuse glioma cohort including also IDH-mutant astrocytomas and oligodendrogliomas as well as in normal brain samples from the Genotype-Tissue Expression cohort. All of the 22 lncRNAs were clearly upregulated in diffuse gliomas samples compared to the normal brain. Interestingly, 20 (91%) of these lncRNAs had significant expression differences between tumor grades and/or entities, and 14 (64%) were associated with overall patient survival. All 22 lncRNAs were expressed in at least one of the studied GBM cell lines and 10 (45%) were expressed in all four. When six of the lncRNAs were silenced in the SNB19 GBM cell line, the knock-down was associated with reduced growth and colony formation for three lncRNAs: TCONS_l2_00001282, lnc-GBMT-6, and lnc-NBN-1. In conclusion, the studied lncRNAs are associated with survival in patients with diffuse glioma and have functional relevance in GBM.

Architectural RNAs (arcRNAs) are long noncoding RNAs that serve as structural scaffolds for membraneless organelles (MLOs), facilitating cellular organization and dynamic responses to stimuli. Acting as blueprints for MLO assembly, arcRNAs recruit specific proteins and nucleic acids to establish and maintain the internal structure of MLOs while coordinating their spatial relationships with other organelles. This organized framework enables precise spatiotemporal regulation, allowing for targeted control of transcription, RNA processing, and cellular responses to stress. Notably, arcRNAs exhibit the "semi-extractable" feature, a property derived from their stable binding to cellular structures, making them partially resistant to conventional RNA extraction methods. This unique feature serves as a useful criterion for identifying novel arcRNAs, providing an opportunity to accelerate research in long noncoding RNAs and deepen our understanding of their functional roles in cellular processes.

The gut microbiota features an abundance of diverse microorganisms and represents an important component of human physiology and metabolic homeostasis, indicating their roles in a wide array of physiological and pathological processes in the host. Maintaining balance in the gut microbiota is critical for normal functionality as microbial dysbiosis can lead to the occurrence and development of diseases through various mechanisms. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are non-coding RNAs that perform important regulatory functions for many processes. Furthermore, the gut microbiota and lncRNAs/circRNAs are known to interact in a range of both physiological and pathological activities. In this article, we review existing research relevant to the interaction between the gut microbiota and lncRNAs/circRNAs and investigate the role of their crosstalk in the pathogenesis of different diseases. Studies have shown that, the gut microbiota can target lncRNAs ENO1-IT1, BFAL1, and LINC00152 to regulate colorectal cancer development via various signaling pathways. In addition, the gut microbiota can influence mental diseases and lung tumor metastasis by modulating circRNAs such as circNF1-419, circ_0001239, circHIPK2 and mmu_circ_0000730. These findings provide a theoretical basis for disease prevention and treatment and suggest that gut microbiota-lncRNA/circRNA crosstalk has high clinical value.

Despite significant advances in cardiology over the past few decades, cardiovascular diseases (CVDs) remain the leading cause of global mortality and morbidity. This underscores the need for novel therapeutic interventions that go beyond symptom management to address the underlying causal mechanisms of CVDs. RNA-based therapeutics represent a new class of drugs capable of regulating specific genetic and molecular pathways, positioning them as strong candidates for targeting the root causes of a wide range of diseases. Moreover, owing to the vast diversity in RNA form and function, these molecules can be utilized to induce changes at different levels of gene expression regulation, making them suitable for a broad array of medical applications, even within a single disease context. Several RNA-based therapies are currently being investigated for their potential to address various CVD pathologies. These include treatments aimed at promoting cardiac revascularization and regeneration, preventing cardiomyocyte apoptosis, reducing harmful circulating cholesterols and fats, lowering blood pressure, reversing cardiac fibrosis and remodeling, and correcting the genetic basis of inherited CVDs. In this review, we discuss the current landscape of RNA therapeutics for CVDs, with an emphasis on their classifications, modes of action, advancements in delivery strategies and considerations for their implementation, as well as CVD targets with proven therapeutic potential.

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer, accounting for 90% of all cases. Currently, early diagnosis of HCC can be achieved through serum alpha-fetoprotein detection, B-ultrasound, and computed tomography scanning; however, their specificity and sensitivity are suboptimal. Despite significant advancements in HCC biomarker detection, the prognosis for patients with HCC remains unfavorable due to tumor heterogeneity and limited understanding of its pathogenesis. Therefore, it is crucial to explore more sensitive HCC biomarkers for improved diagnosis, monitoring, and management of the disease. Long non-coding RNA (lncRNA) serves as an auxiliary carrier of genetic information and also plays diverse intricate regulatory roles that greatly contribute to genome complexity. Moreover, investigating gene expression regulation networks from the perspective of lncRNA may provide insights into the diagnosis and prognosis of HCC. We searched the PubMed database for literature, comprehensively classified regulated cell death mechanisms and systematically reviewed research progress on lncRNA-mediated cell death pathways in HCC cells. Furthermore, we prospectively summarize its potential implications in diagnosing and treating HCC.

Long non-coding RNAs (lncRNAs) are a regulatory feature that have been reported to operate on both transcriptional and translational levels. With DNA-based prediction still limited, lncRNAs are most reliably identified through genome-guided mapping of RNA-Seq data. Reports of lncRNAs in yeast have been increasing in recent years and changes in their expression levels have often been associated with stressful conditions. As the transition to near zero-growth conditions likely imposes stress, we used RNA-Seq data from the non-conventional, biotechnologically established yeast Komagataella phaffii, cultivated in glucose-limited retentostats, to identify the expression of lncRNAs. Using an adapted bioinformatics pipeline, we identified 168 mostly novel lncRNAs from the K. phaffii retentostat RNA-Seq data, 36 of which demonstrate likely growth-associated expression changes. lncRNA expression levels were associated to that of possible interaction partners, in both cis and trans, suggesting potential roles in regulatory adaptations. Our analysis indicates that lncRNAs likely contribute to how K. phaffii responds to changing environmental conditions, as exemplified here by the adaptation to extremely slow growth.

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.

Emerging research suggests that dysregulation of long non-coding RNAs (lncRNAs) is closely linked to the onset and progression of cancer. In this study, we used lncRNA array technology to identify differentially expressed lncRNAs in lung adenocarcinoma patients and normal lung tissues. The study further explored the clinical significance and function of candidate lncRNAs in lung adenocarcinoma (LUAD). The results showed that lncRNA NR_146969 was upregulated in LAUD specimens and was associated with lymph node metastasis and clinical staging in LUAD patients.

The biological functions of lncRNA NR_146969 were observed using CCK-8, colony formation, transwell assay and xenograft tumor model. Explore the potential mechanism of action of lncRNA NR_146969 by FISH, dual luciferase reporter assay and recovery assay.

Overall, lncRNA NR_146969 plays an oncogenic role in LUAD. Mechanically, lncRNA NR_146969 targets SLC6A14 via miR-26a-1-3p, leading to phosphorylation of the AKT/mTOR pathway, which promotes LUAD growth and metastasis.

Therefore, targeting lncRNA NR_146969 may provide a new therapeutic strategy for LUAD.

The microbiome of the gut is a complex ecosystem that contains a wide variety of microbial species and functional capabilities. The microbiome has a significant impact on health and disease by affecting endocrinology, physiology, and neurology. It can change the progression of certain diseases and enhance treatment responses and tolerance. The gut microbiota plays a pivotal role in human health, influencing a wide range of physiological processes. Recent advances in computational tools and artificial intelligence (AI) have revolutionized the study of gut microbiota, enabling the identification of biomarkers that are critical for diagnosing and treating various diseases. This review hunts through the cutting-edge computational methodologies that integrate multi-omics data-such as metagenomics, metaproteomics, and metabolomics-providing a comprehensive understanding of the gut microbiome's composition and function. Additionally, machine learning (ML) approaches, including deep learning and network-based methods, are explored for their ability to uncover complex patterns within microbiome data, offering unprecedented insights into microbial interactions and their link to host health. By highlighting the synergy between traditional bioinformatics tools and advanced AI techniques, this review underscores the potential of these approaches in enhancing biomarker discovery and developing personalized therapeutic strategies. The convergence of computational advancements and microbiome research marks a significant step forward in precision medicine, paving the way for novel diagnostics and treatments tailored to individual microbiome profiles. Investigators have the ability to discover connections between the composition of microorganisms, the expression of genes, and the profiles of metabolites. Individual reactions to medicines that target gut microbes can be predicted by models driven by artificial intelligence. It is possible to obtain personalized and precision medicine by first gaining an understanding of the impact that the gut microbiota has on the development of disease. The application of machine learning allows for the customization of treatments to the specific microbial environment of an individual.

Several studies have made it possible to envision a translational application of plasma DNA sequencing in cancer diagnosis and monitoring. However, the extremely low concentration of circulating tumour DNA (ctDNA) fragments among the total cell-free DNA (cfDNA) remains a formidable challenge to overcome and statistical models have yet to be improved enough to become of practical use. In this study, we set about appraising the predictive value of a variety of binary classification models based on cfDNA sequencing using fragmentation features extracted around transcription start sites (TSSs). We investigated (1) features summarising mapped fragment density around each TSS, (2) long non-coding RNA (lncRNA) genes versus coding genes and (3) selection criteria to generate gene classes to be assigned by the model. Given that, in healthy samples, most of the cfDNA comes from lymphomyeloid lineages, we could identify the model parametrisation with the best accuracy in those lineages using publicly available datasets of healthy patients' cfDNA. Our results show that (1) the way tissue-specific gene classes are defined matters more than what fragmentation features are included, and (2) in particular, lncRNAs are more tissue specific than coding genes and stand out in terms of both sensitivity and specificity in our results.

The human genome sequencing revealed a vast complexity of transcripts, with over 80% of the genome being transcribed into non-coding RNAs. In particular, long non-coding RNAs (lncRNAs) have emerged as critical regulators of various cellular processes, including embryonic development and stem cell differentiation. Despite extensive efforts to identify and characterize lncRNAs, defining their mechanisms of action in state-specific cellular contexts remains a significant challenge. Only recently has the involvement of lncRNAs in human endoderm differentiation of pluripotent stem cells begun to be addressed, creating an opportunity to explore the mechanisms by which lncRNAs exert their functions in germ layer formation, lineage specification, and commitment. This review summarizes current findings on the roles of lncRNAs in endoderm differentiation, highlighting the functional mechanisms and regulatory aspects underlying their involvement in cell fate decisions leading to endoderm development. The key lncRNAs implicated in endoderm differentiation are discussed, along with their interaction with transcription factors and RNA-binding proteins and modulation of signaling pathways essential for endoderm development. Gaining insight into the regulatory roles of lncRNAs in endoderm differentiation enhances the understanding of developmental biology and provides a foundation for discovering novel lncRNAs involved in cell fate determination.

Glioblastoma (GBM) is the most prevalent and aggressive primary central nervous system (CNS) tumor in adults. GBMs exhibit genetic and epigenetic heterogeneity, posing difficulties in surveillance and being associated with high rates of recurrence and mortality. Nevertheless, due to the high infiltrating ability of glioblastoma cells, and regardless of the considerable progress made in radiotherapeutic, chemotherapeutic, and surgical protocols, the treatment of GBM is still inefficient. Conventional diagnostic approaches, such as neuroimaging techniques and tissue biopsies, which are invasive maneuvers, present certain challenges and limitations in providing real-time information, and are incapable of differentiating pseudo-progression related to treatment from real tumor progression. Liquid biopsy, the analysis of biomarkers such as nucleic acids (DNA/RNA), circulating tumor cells (CTCs), extracellular vesicles (EVs), or tumor-educated platelets (TEPs) that are present in body fluids, provides a minimally invasive and dynamic method of diagnosis and continuous monitoring for GBM. It represents a new preferred approach that enables a superior manner to obtain data on possible tumor risk, prognosis, and recurrence assessment. This article is a literature review that aims to provide updated information about GBM biomarkers in body fluids and to analyze their clinical efficiency.

Neurons are highly polarized, specialized cells that must overcome immense challenges to ensure the health and survival of the organism in which they reside. They can spread over meters and persist for decades yet communicate at sub-millisecond and millimeter scales. Thus, neurons require extreme levels of spatial-temporal control. Neurons employ molecular motors to transport coding and noncoding RNAs to distal synapses. Intracellular trafficking of RNAs enables neurons to locally regulate protein synthesis and synaptic activity. The way in which RNAs get loaded onto molecular motors and transported to their target locations, particularly following synaptic plasticity, is explored below.

Neuropathic pain (NeP) is a most intractable health problem due to its unsatisfactory treatment effect. Emodin, a natural anthraquinone derivative extracted from Rheum palmatum and Polygonam cuspidatum, exhibits the analgesic effects in various NeP models. However, the underlying mechanisms remain elusive. This study employed whole transcriptome sequencing and metabolomics to elucidate emodin's analgesic mechanism in the spinal cord of chronic constriction injury (CCI) rats. Fifteen-day emodin treatment reversed hyperalgesia and deficit of sciatic nerve function induced by CCI and significantly decreased the concentrations of TNF-α, IL- 1β, IL- 6, IL- 18, and BDNF in the spinal cord of the CCI rats. Transcriptome sequencing revealed altered expression of 85 mRNAs in the spinal cord of emodin-treated and CCI rats, with 53 mRNAs upregulated and 32 mRNAs downregulated. Notably, seven genes (P2RX4, CXCL10, ALOX5, SCN4 A, AURKB, AQP9) overlapped with established NeP targets. Untargeted metabolomic analyses identified 67 significantly altered metabolites (46 upregulated, 32 downregulated) in the spinal cord upon emodin treatment. Integrative analysis highlighted shared pathways between differentially expressed genes and metabolites, including arachidonic acid metabolism, cAMP signaling pathway, and Fc epsilon RI signaling pathway. Western blot and immunofluorescent staining further proved the decreased expression of IBA1, P2X4R, p38 MAPK, p-p38 MAPK, NF-κB, p-NF-κB, and TNF-α, IL- 1β. In conclusion, this study demonstrated that emodin played the analgesic effect in the CCI rats, possibly through suppression of P2X4 purinoceptor signaling in spinal microglia, suggesting a potential therapeutic target for NeP.

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.

Bats possess a uniquely adapted immune system that enables them to live with viral infections without the expected maladies. The molecular basis and regulation of bats' immune response is still not fully understood. Long non-coding RNAs (lncRNAs) represent an emerging class of molecules with critical regulatory roles in multiple biological processes, including immunity. We hypothesise that lncRNA-based regulation in bats may enable them to limit disease and live with viral pathogens.

We developed a lncRNA prediction pipeline to annotate the long non-coding transcriptome across multiple bat tissues and at the population level. Characterisation of our lncRNA dataset based on 100 blood transcriptomes from wild Myotis myotis bats revealed lower and more tissue-specific expression compared with coding genes, reduced GC content and shorter length distributions, consistent with lncRNA profiles observed in other species. Using WGCNA network analyses and gene ontology, we identified two mRNA-lncRNA co-expression modules in Myotis myotis associated with distinct immune response: one linked to T-cell activation and vial processes, and the other to inflammation. From these immune-related lncRNAs, we selected four candidates with high translational potential for regulating viral infections and inflammation. These include a newly identified lncRNA, BatLnc1, with potential antiviral functions; the M. myotis ortholog of TUG1, implicated in viral-host interactions; and well-known lncRNAs MALAT1 and NEAT1, recognised for their roles in inflammatory regulation.

We conducted the first ab initio prediction of lncRNAs in a non-model bat species, the wild-caught M. myotis. Our network analysis revealed significant variation in immune status among a subset of individuals, potentially due to pathogenic conditions. From these variations, we identified lncRNAs most likely associated with immune response in bats. This initial exploration lays the groundwork for future experimental validations of lncRNA functions, offering promising insights into their role in bat immunity.

Clove (Syzygium aromaticum), valued for its role in food preservation and medicine, has recently drawn research interest for its noncoding RNAs (ncRNAs). This study discovers 3274 long noncoding RNAs (lncRNAs) and 2404 circular RNAs (circRNAs) from publicly available RNAseq data. We identified the regulation of 834 genes through miRNA-lncRNA-mRNA network interactions. Additionally, 35 lncRNAs were predicted as precursors for 17 microRNAs (miRNAs), highlighting their role in post-transcriptional regulation. Tissue-specific analysis of circRNAs revealed their interaction with 1047 miRNAs and competing for binding sites on 2382 messenger RNAs (mRNAs). These results underscore their involvement in complex regulatory networks. To support further research and development, we developed SaroNcRDb (http://backlin.cabgrid.res.in/saroncrdb/), a web resource providing detailed insights into the types, chromosomal locations, tissue distributions, and interactions of identified ncRNAs. The findings pave the way for future studies to harness the regulatory roles of ncRNAs in improving Clove's agronomic traits and secondary metabolite production.

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.

ObjectiveThe current study aimed to investigate the role of the myocardial infarction-associated transcript (MIAT)/microRNA-326 (miR-326) axis in regulating the migration of vascular smooth muscle cells (VSMCs) during the progression of atherosclerosis (AS).MethodsBioinformatic analysis of MIAT and miR-326 in two AS-related GEO datasets was performed via the online web tool GEO2R. MIAT and miR-326 expression in 46 paired plasma samples and in oxidized low-density lipoprotein (ox-LDL)-treated VSMCs was analysed via RT-qPCR. Western blot analysis was used to determine the expression of monocyte chemotactic protein 1 (MCP-1) after diverse ox-LDL treatments. The correlation between MIAT and miR-326 was analysed by Spearman correlation analysis. Transwell assays were performed to determine the changes in migration after different MIAT or miR-326 interventions. RNA-fluorescence in situ hybridization (FISH) assays were performed to determine the subcellular localization of MIAT and miR-326. The targeted binding effect between MIAT and miR-326 was confirmed via a luciferase assay.ResultsMIAT was upregulated and miR-326 was downregulated in 46 plasma samples from patients with AS compared with those from patients without AS (non-AS). A negative correlation was found between MIAT and miR-326 (r = - 0.6591, P < 0.0001). The expression of MIAT in plaque samples from advanced AS patients was markedly greater than that in plaque samples from early AS patients according to the GEO dataset GSE28829 (P < 0.0001). The expression of miR-326 in platelet samples from patients with first acute myocardial infarction (FAMI) was significantly lower than that in healthy controls (P = 0.0034). MCP-1 was upregulated in ox-LDL-treated VSMCs. MIAT knockdown by specific MIAT small interfering RNAs (siRNAs) suppressed VSMC migration. Upregulation of miR-326 by transfection of miR-326 mimics also inhibited VSMC migration. Dual luciferase assays indicated that miR-326 targets MIAT. The upregulation of MIAT increased the migration of VSMCs. However, this effect was attenuated by a miR-326 mimic.ConclusionsMIAT was upregulated and miR-326 was downregulated in AS plasma and in ox-LDL-treated VSMCs. MIAT binds to miR-326 via theoretical miRNA response elements. MIAT promoted migration by sponging miR-326 in ox-LDL-induced VMSCs. The MIAT/miR-326 axis may represent a novel therapeutic target for the treatment of AS, offering potential insights into AS progression and its clinical management.

Long noncoding RNAs (lncRNAs) are important regulators of gene expression. Although evidence accumulated over the past decade shows that lncRNAs have key roles in the interaction between viruses and hosts, the functions of the majority of differentially expressed lncRNAs in response to viral infections remain uncharacterized so far. In this study, we have identified that USP30 antisense RNA 1 (USP30-AS1), a host antisense lncRNA, is hijacked by influenza A virus (IAV) to assist its replication. We show that USP30-AS1 is IAV-induced via the Janus protein tyrosine kinase-signal transducer and the activator of transcription (JAK-STAT) signaling pathway. Functionally, ectopic expression of USP30-AS1 significantly promotes IAV replication. Conversely, silencing USP30-AS1 suppresses IAV replication. Mechanistically, USP30-AS1 directly binds prohibitin 1 (PHB1) and modulates its protein stability and function. On the one hand, the binding of USP30-AS1 sequesters PHB1 away from the E3 ubiquitin ligase, tripartite motif containing 21 (TRIM21), thereby protecting the protein stability of PHB1. On the other hand, USP30-AS1 serves as a molecular scaffold for enhancing the interaction between PHB1 and interferon regulatory factor 3 (IRF3), which in turn impedes the nuclear import of IRF3. Therefore, our data unveil an important role of USP30-AS1 in promoting viral replication by modulating PHB1 stability and functions, providing a new insight into the role of lncRNAs in the interplay between IAV and host.

Periodontal ligament stem cells (PDLSCs) are key cells that suppress periodontal damage during both the progression and recovery stages of periodontitis. Although substantial evidence has demonstrated that incubation under an inflammatory condition may accelerate senescence of PDLSCs, whether cellular senescence in response to inflammatory incubation contributes to cell dysfunction remain unexplored. In this study, we first observed inflammation-caused PDLSC senescence in periodontitis based on comparisons of matched patients, and this cellular senescence was demonstrated in healthy cells that were subjected to inflammatory conditions. We subsequently designed further experiments to investigate the possible mechanism underlying inflammation-induced PDLSC senescence with a particular focus on the role of long noncoding RNAs (lncRNAs). LncRNA microarray analysis and functional gain/loss studies revealed SLC30A4-AS1 as a regulator of inflammation-mediated PDLSC senescence. By full-length transcriptome sequencing, we found that SLC30A4-AS1 interacted with SRSF3 to affect the alternative splicing (AS) of TP53BP1 and alter the expression of TP53BP1-204. Further functional studies showed that decreased expression of TP53BP1-204 reversed PDLSC senescence, and SLC30A4-AS1 overexpression-induced PDLSC senescence was abolished by TP53BP1-204 knockdown. Our data suggest for the first time that SLC30A4-AS1 plays a key role in regulating PDLSC senescence in inflammatory environments by modulating the AS of TP53BP1.

In this study, we analyze the long noncoding RNA, lncMN3, that is predominantly expressed in motor neurons and shows potential coding capabilities. Utilizing custom antibodies, we demonstrate the production of a lncMN3-derived type I transmembrane micropeptide, SERTM2. Patch-clamp experiments performed on both wild-type and SERTM2 knockout motor neurons, differentiated in vitro from mouse embryonic stem cells, show a difference in the resting membrane potential and overall decreased excitability upon SERTM2 depletion. In vivo studies indicate that the absence of the peptide impairs treadmill test performance. At the mechanistic level, we identify a two-pore domain potassium channel, TASK1, known to be a major determinant of the resting membrane potential in motor neurons, as a SERTM2 interactor. Our study characterizes one of the first lncRNA-derived micropeptides involved in neuronal physiology.

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.

Accumulated studies have demonstrated that long noncoding RNAs (lncRNAs) play crucial regulatory roles in diverse biological processes, such as embryonic development and cell differentiation. Comprehensive transcriptome analysis identifies extensive lncRNAs, gradually elucidating their functions across various contexts. Recent studies have highlighted the essential role of lncRNAs in definitive endoderm differentiation, underscoring their importance in early development. In this review, we have analyzed the features of overlapping, proximal, and desert lncRNAs, classified by genomic location, in pluripotent stem cells (PSCs) and the differentiation derivatives. Furthermore, we focus on the endoderm lineage and review the latest advancements in lncRNA identification and their distinct regulatory mechanisms. By consolidating current knowledge, we aim to provide a clearer perspective on how lncRNAs contribute to endoderm differentiation in different manners.

The bulk of RNA produced from the genome of complex organisms consists of a very large number of transcripts lacking protein translational potential and collectively known as noncoding RNAs (ncRNAs). Initially thought to be mere products of spurious transcriptional noise, ncRNAs are now universally recognized as pivotal players in cell regulatory networks across a broad spectrum of biological processes. Owing to their critical regulatory roles, ncRNA dysfunction is closely associated with the etiopathogenesis of various human malignancies, including cancer. As such, ncRNAs represent valuable diagnostic biomarkers as well as potential targets for innovative therapeutic intervention. In this review, we focus on microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), the two most extensively studied classes in the field of ncRNA biology. After outlining key concepts of miRNA and lncRNA biogenesis pathways, we examine their multiple roles in mediating epigenetic regulation of gene expression and chromatin organization. Finally, by providing numerous examples of specific miRNAs and lncRNAs, we discuss how dysregulation of these mechanisms contributes to the onset and/or progression of various human diseases.

Aberrant Wnt pathway activation is a key driver of colorectal cancer (CRC) and is essential to sustain tumour growth and progression. Although the downstream protein-coding target genes of the Wnt cascade are well known, the long non-coding transcriptome has not yet been fully resolved.

In this study, we aim to comprehensively reveal the Wnt-regulated long non-coding transcriptome and exploit essential molecules as novel therapeutic targets.

We used global run-on sequencing to define β-catenin-regulated long non-coding RNAs (lncRNAs) in CRC. CRISPRi dropout screens were subsequently used to establish the functional relevance of a subset of these lncRNAs for long-term expansion of CRC.

We uncovered that LINC02418 is essential for cancer cell clonogenic outgrowth. Mechanistically, LINC02418 regulates MYC expression levels to promote CRC stem cell functionality and prevent terminal differentiation. Furthermore, we developed effective small interfering RNA (siRNA)-based therapeutics to target LINC02418 RNA in vivo.

We propose that cancer-specific Wnt-regulated lncRNAs provide novel therapeutic opportunities to interfere with the Wnt pathway, which has so far defied effective pharmacological inhibition.

Long non-coding RNAs (lncRNAs), a type of non-coding RNA molecules, are known to play critical regulatory roles in various biological processes. However, the functions of the majority of lncRNAs remain largely unknown, and little is understood about the regulation of lncRNA expression. In this study, high-throughput DNA genotyping and RNA sequencing were applied to investigate genomic regions associated with lncRNA expression, commonly referred to as lncRNA expression quantitative trait loci (eQTLs). We analyzed the liver, lung, spleen, and muscle transcriptomes of 100 three-way crossbred sows to identify lncRNA transcripts, explore genomic regions that might influence lncRNA expression, and identify potential regulators interacting with these regions.

We identified 6380 lncRNA transcripts and 3733 lncRNA genes. Correlation tests between the expression of lncRNAs and protein-coding genes were performed. Subsequently, functional enrichment analyses were carried out on protein-coding genes highly correlated with lncRNAs. Our correlation results of these protein-coding genes uncovered terms that are related to tissue specific functions. Additionally, heatmaps of lncRNAs and protein-coding genes at different correlation levels revealed several distinct clusters. An expression genome-wide association study (eGWAS) was conducted using 535,896 genotypes and 1829, 1944, 2089, and 2074 expressed lncRNA genes for liver, spleen, lung, and muscle, respectively. This analysis identified 520,562 significant associations and 6654, 4525, 4842, and 7125 eQTLs for the respective tissues. Only a small portion of these eQTLs were classified as cis-eQTLs. Fifteen regions with the highest eQTL density were selected as eGWAS hotspots and potential mechanisms of lncRNA regulation in these hotspots were explored. However, we did not identify any interactions between the transcription factors or miRNAs in the hotspots and the lncRNAs, nor did we observe a significant enrichment of regulatory elements in these hotspots. While we could not pinpoint the key factors regulating lncRNA expression, our results suggest that the regulation of lncRNAs involves more complex mechanisms.

Our findings provide insights into several features and potential functions of lncRNAs in various tissues. However, the mechanisms by which lncRNA eQTLs regulate lncRNA expression remain unclear. Further research is needed to explore the regulation of lncRNA expression and the mechanisms underlying lncRNA interactions with small molecules and regulatory proteins.

Eukaryotic cells are highly structured and composed of multiple membrane-bound and membraneless organelles. Subcellular RNA localization is a critical regulator of RNA function, influencing various biological processes. At any given moment, RNAs must accurately navigate the three-dimensional subcellular environment to ensure proper localization and function, governed by numerous factors, including splicing, RNA stability, modifications, and localizing sequences. Aberrant RNA localization can contribute to the development of numerous diseases. Here, we explore diverse RNA localization mechanisms and summarize advancements in methods for determining subcellular RNA localization, highlighting imaging techniques transforming our ability to study RNA dynamics at the single-molecule level.

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.

Fibrosis is the common end point for all forms of chronic liver injury, and the progression of fibrosis leads to the development of end-stage liver disease. Activation of HSCs and their transdifferentiation into myofibroblasts results in the accumulation of extracellular matrix proteins that form the fibrotic scar. Long noncoding RNAs regulate the activity of HSCs and provide targets for fibrotic therapies.

We identified long noncoding RNA TILAM located near COL1A1 , expressed in HSCs, and induced with liver fibrosis in humans and mice. Loss-of-function studies in human HSCs and human liver organoids revealed that TILAM regulates the expression of COL1A1 and other extracellular matrix genes. To determine the role of TILAM in vivo, we annotated the mouse ortholog ( Tilam ), generated Tilam- deficient green fluorescent protein-reporter mice, and challenged these mice in 2 different models of liver fibrosis. Single-cell data and analysis of single-data and analysis of Tilam-deficient reporter mice revealed that Tilam is induced in murine HSCs with the development of fibrosis in vivo. Tilam -deficient reporter mice revealed that Tilam is induced in murine HSCs with the development of fibrosis in vivo. Furthermore, loss of Tilam expression attenuated the development of fibrosis in the setting of in vivo liver injury. Finally, we found that TILAM interacts with promyelocytic leukemia nuclear body scaffold protein to regulate a feedback loop by which TGF-β2 reinforces TILAM expression and nuclear localization of promyelocytic leukemia nuclear body scaffold protein to promote the fibrotic activity of HSCs.

TILAM is activated in HSCs with liver injury and interacts with promyelocytic leukemia nuclear body scaffold protein to drive the development of fibrosis. Depletion of TILAM may serve as a therapeutic approach to combat the development of end-stage liver disease.

PVT1 exon 9 overexpression is a newly uncovered aberration in prostate cancer (PCa). We have previously demonstrated the exon 9 region of PVT1 is overexpressed in some patient PCa tissues and caused development of neuroendocrine prostate cancer (NEPC) in vitro and in vivo. In this study, we focused on elucidating downstream mechanisms induced by PVT1 exon 9 overexpression with the goal of further understanding its role in NEPC development. RNA-seq analysis of a PVT1 exon 9 overexpressing PCa model revealed significant enrichment of genes responsible for inducing inflammatory processes including RSAD2. We observed RSAD2 overexpression in all NEPC models examined whereas PVT1 exon 9 was overexpressed only in a subset of the NEPC models. We identified two distinct pathways in which RSAD2 is overexpressed: one dependent and one independent on PVT1 exon 9 overexpression. Knockdown of RSAD2 suppressed cell proliferation and migration suggestive of its role as a therapeutic target in NEPC. We identified RSAD2 induces increased cell proliferation, colony formation, and may be involved in the transition between CRPC and NEPC. Distinct differences between PVT1 exon 9-dependent and PVT1 exon 9-independent NEPC models include differences in type II interferon signaling and AR modulation. PVT1 exon 9 binds to RSAD2 protein and disruption of binding significantly impedes downstream interferon gamma secretion by PVT1 exon 9-dependent NEPC cells. These novel findings indicate the importance of these two independent pathways in NEPC, the need to identify relevant NEPC patient populations and study strategies for targeting PVT1 exon 9 and/or RSAD2.

Drug resistance is a prevalent challenge in clinical disease treatment, often leading to disease relapse and poor prognosis. Therefore, it is crucial to gain a deeper understanding of the molecular mechanisms underlying drug resistance and to develop targeted strategies for its effective prevention and management. Mitochondria, as vital energy-producing organelles within cells, have been recognized as key regulators of drug sensitivity. Processes such as mitochondrial fission, fusion, mitophagy, changes in membrane potential, reactive oxygen species (ROS) accumulation, and oxidative phosphorylation (OXPHOS) are all linked to drug sensitivity. Non-coding RNAs (ncRNAs) enriched in mitochondria (mtncRNA), whether transcribed from mitochondrial DNA (mtDNA) or from the nucleus and transported to mitochondria, can regulate the transcription and translation of mtDNA, thus influencing mitochondrial function, including mitochondrial substance exchange and energy metabolism. This, in turn, directly or indirectly affects cellular sensitivity to drugs. This review summarizes the types of mtncRNAs associated with drug resistance and the molecular mechanisms regulating drug resistance. Our aim is to provide insights and strategies for overcoming drug resistance by modulating mtncRNAs.

This review explores the intricate landscape of neurodegenerative disease research, focusing on Amyotrophic Lateral Sclerosis (ALS) and the intersection of genetics and RNA biology to investigate the causative pathogenetic basis of this fatal disease. ALS is a severe neurodegenerative disease characterized by the progressive loss of motor neurons, leading to muscle weakness and paralysis. Despite significant research advances, the exact cause of ALS remains largely unknown. Thanks to the application of next-generation sequencing (NGS) approaches, it was possible to highlight the fundamental role of rare variants with large effect sizes and involvement of portions of non-coding RNA, providing valuable information on risk prediction, diagnosis, and treatment of age-related diseases, such as ALS. Genetic research has provided valuable insights into the pathophysiology of ALS, leading to the development of targeted therapies such as antisense oligonucleotides (ASOs). Regulatory agencies in several countries are evaluating the commercialization of Qalsody (Tofersen) for SOD1-associated ALS, highlighting the potential of gene-targeted therapies. Furthermore, the emerging significance of microRNAs (miRNAs) and long RNAs are of great interest. MiRNAs have emerged as promising biomarkers for diagnosing ALS and monitoring disease progression. Understanding the role of lncRNAs in the pathogenesis of ALS opens new avenues for therapeutic intervention. However, challenges remain in delivering RNA-based therapeutics to the central nervous system. Advances in genetic screening and personalized medicine hold promise for improving the management of ALS. Ongoing clinical trials use genomic approaches for patient stratification and drug targeting. Further research into the role of non-coding RNAs in the pathogenesis of ALS and their potential as therapeutic targets is crucial to the development of effective treatments for this devastating disease.

tRNA-derived small RNA (tsRNA) is a recently discovered small non-coding RNA (ncRNA) molecule that widely exists in prokaryotic and eukaryotic transcriptomes and is produced by specific cleavage of mature tRNA or precursor tRNA. In recent years, with the development of high-throughput sequencing technology, tsRNA has been found to have a variety of biological functions, including gene expression regulation, stress signal activation, etc. In addition, it has been found that these molecules are abnormally expressed in various diseases and participate in various pathological processes, which play an important role. At present, more and more studies have shown that the expression level of tsRNA changes significantly during the development of neurogenetic diseases. This review provides an overview of the classification and biological functions of tsRNAs, with a particular emphasis on their roles in neurogenetic disorders and their potential as diagnostic biomarkers and therapeutic targets. Despite the nascent stage of tsRNA research, their relevance to the diagnosis and treatment of neurogenetic diseases warrants further investigation.

While apoptotic cell death is known to be central to the pathogenesis of radiation-induced liver injury (RILI), the mechanistic basis for this apoptotic activity remains poorly understood. N6-methyladenosine (m6A) modifications are the most common form of reversible methylation observed on lncRNAs in eukaryotic cells, with their presence leading to pronounced changes in the activity of a range of biological processes. The degree to which m6A modification plays a role in the induction of apoptotic cell death in response to ionizing radiation (IR) in the context of RILI remains to be established. Here, IR-induced apoptosis was found to significantly decrease the levels of m6A present, with a pronounced decrease in the expression of methyltransferase-like 3 (METTL3) at 2 d post radiation in vitro. From a mechanistic perspective, a methylated RNA immunoprecipitation assay found that lncRNA MEG3 was a major METTL3 target. The expression of MEG3 was upregulated via METTL3-mediated m6A in a process that was dependent on YTHDC1, ultimately reversing the miR-20b-mediated inhibition of BNIP2 expression. Together, these findings demonstrate that the responsivity of METTL3 activity to IR plays a role in IR-induced apoptotic cell death, leading to the reverse of miR-20b-mediated BNIP2 inhibition through the YTHDC1-dependent m6A modification of MEG3, suggesting that this process may play a central role in RILI incidence.

Glioblastoma (GBM) is a highly aggressive and treatment-resistant brain tumor. Recent advancements have highlighted the crucial role of long noncoding RNAs (lncRNAs) in GBM's molecular biology. Unlike protein-coding RNAs, lncRNAs regulate gene expression through transcription, post-transcriptional modifications, and chromatin remodeling. Some lncRNAs, like HOTAIR, CCAT2, CRNDE, and MALAT1, promote GBM development by affecting tumor suppressors and various signaling pathways like PI3K/Akt, mTOR, EGFR, NF-κB, and Wnt/β-catenin. Conversely, certain lncRNAs such as TUG1, MEG3, and GAS8-AS1 act as tumor suppressors and are associated with better prognosis. The study presented in the manuscript aims to explore the involvement of lncRNAs in GBM, focusing on their roles in tumor progression, proliferation, invasion, and potential implications for early detection and immunotherapy. The research seeks to elucidate the mechanisms by which specific lncRNAs influence GBM characteristics and highlight their potential as therapeutic targets or biomarkers in managing this aggressive form of brain cancer.

Rapid identification of acute ischemic stroke (AIS) is challenging in both pre-hospital and hospital settings. We aimed to identify the most promising cell-free nucleic acids (cfNAs) as diagnostic biomarkers for IS within 72 h from symptom onset. We searched PubMed, Web of Science, EMBASE, and Cochrane Library for published articles that evaluated blood cfNAs in the early diagnosis of AIS until 10 May 2023. The diagnostic performances of individual cfNAs were pooled by random-effects meta-analysis based on the fold change of biomarkers' level between AIS and non-AIS patients. Of 2955 records, 66 articles reporting 143 different cfNAs met the inclusion criteria. The median sample size was 110, and 21.4% of the studies performed validation. Among selected high-quality studies, miR-106b-5p, miR-124, miR-155, lncRNA H19, and cfDNA showed good diagnostic performance. Data from four studies on cfDNA involving 355 AIS patients and 97 controls were pooled in the meta-analysis, which showed a significant fold change between AIS and controls (pooled ratio 1.48, 95% confidence interval 1.23-1.79, p < 0.001). This review highlights that cfDNA, miR-106b-5p, miR-124, miR-155, and lncRNA H19 are the most promising biomarkers for AIS diagnosis, and further research is needed for verification.