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In experiments dubbed the Random Genome Project, researchers have integrated DNA strands with random sequences into yeast and mouse cells to find the default transcriptional state of their genomes. Yeast and mammalian genomes have different default transcriptional states. [ABSTRACT FROM AUTHOR]

Depression, a significant mental health disorder, is under intense research scrutiny to uncover its molecular foundations. Epigenetics, which focuses on controlling gene expression without altering DNA sequences, offers promising avenues for innovative treatment. This review explores the pivotal role of epigenetics in depression, emphasizing two key aspects: (I) identifying epigenetic targets for new antidepressants and (II) using personalized medicine based on distinct epigenetic profiles, highlighting potential epigenetic focal points such as DNA methylation, histone structure alterations, and non-coding RNA molecules such as miRNAs. Variations in DNA methylation in individuals with depression provide opportunities to target genes that are associated with neuroplasticity and synaptic activity. Aberrant histone acetylation may indicate that antidepressant strategies involve enzyme modifications. Modulating miRNA levels can reshape depression-linked gene expression. The second section discusses personalized medicine based on epigenetic profiles. Analyzing these patterns could identify biomarkers associated with treatment response and susceptibility to depression, facilitating tailored treatments and proactive mental health care. Addressing ethical concerns regarding epigenetic information, such as privacy and stigmatization, is crucial in understanding the biological basis of depression. Therefore, researchers must consider these issues when examining the role of epigenetics in mental health disorders. The importance of epigenetics in depression is a critical aspect of modern medical research. These findings hold great potential for novel antidepressant medications and personalized treatments, which would significantly improve patient outcomes, and transform psychiatry. As research progresses, it is expected to uncover more complex aspects of epigenetic processes associated with depression, enhance our comprehension, and increase the effectiveness of therapies.

Ankylosing spondylitis (AS) is a chronic inflammatory disorder characterized by inflammatory back pain and bony fusion of vertebral joints. Genetic associations and environmental factors have been proposed to explain the immunopathogenesis of AS. In the past few years, there have been major advances in understanding T cell dysfunction in AS. Clinically, targeting interleukin-17A, a major cytokine secreted by T helper 17 cells, has been approved for treating patients with active AS. Non-coding RNAs (ncRNAs) are RNA transcripts that do not translate into proteins. The ncRNAs regulate both innate and adaptive immunity and participate in the pathogenesis of autoimmune diseases, including AS. The main purpose of this article is to review the up-to-date studies investigating the aberrant expression of ncRNAs in T cells from patients with AS and to summarize their roles in its pathogenesis. After searching PubMed for studies published between January 2013 and June 2024, nine studies investigating the expression of ncRNAs in AS T cells were included. We found that aberrantly expressed ncRNAs in AS T cells could cause abnormal cytokine release, cell signaling abnormalities, and dysregulated cell proliferation and death, which contribute to the immunopathogenesis of AS. We discussed some limitations of these studies and suggested several research fields for further investigation.

Metastasis is the primary cause of cancer-related death, with the dissemination and colonization of primary tumor cells at the metastatic site facilitated by various molecules and complex pathways. Understanding the biological mechanisms underlying the metastatic process is critical for the development of effective interventions. Several epigenetic modifications have been identified that play critical roles in regulating cancer metastasis. This review aims to provide a comprehensive summary of recent advances in understanding the role of epigenetic modifiers, including histone modifications, DNA methylation, non-coding RNAs, enhancer reprogramming, chromatin accessibility, and N6-methyladenosine, in metastasis-associated processes, such as epithelial-mesenchymal transition (EMT), cancer cell migration, and invasion. In particular, this review provides a detailed and in-depth description of the role of crosstalk between epigenetic regulators in tumor metastasis. Additionally, we explored the potential and limitations of epigenetics-related target molecules in the diagnosis, treatment, and prognosis of cancer metastasis.

The emergence of cancers involves numerous coding and non-coding genes. Understanding the contribution of non-coding RNAs (ncRNAs) to the cancer neighborhood is crucial for interpreting the interaction between molecular markers of cancer. However, there is a lack of systematic studies on the involvement of ncRNAs in the cancer neighborhood. In this paper, we construct an interaction network which encompasses multiple genes. We focus on the fundamental topological indicator, namely connectivity, and evaluate its performance when applied to cancer-affected genes using statistical indices. Our findings reveal that ncRNAs significantly enhance the connectivity of affected genes and mediate the inclusion of more genes in the cancer module. To further explore the role of ncRNAs in the network, we propose a connectivity-based method which leverages the bridging function of ncRNAs across cancer-affected genes and reveals the non-coding RNAs extended omnigenic module (NeOModule). Topologically, this module promotes the formation of cancer patterns involving ncRNAs. Biologically, it is enriched with cancer pathways and treatment targets, providing valuable insights into disease relationships.

Sjögren’s syndrome is a multisystemic autoimmune disease that mainly affects the exocrine glands, causing dryness of the eyes and the mouth as the principal symptoms. Non-coding RNAs (ncRNAs), once regarded as genomic “junk”, are now appreciated as important molecular regulators of gene expression, not least in Sjögren’s syndrome and other autoimmune diseases. Here we review research into the causative roles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) on immunological responses, inflammation, and salivary gland epithelial cell function in Sjögren’s syndrome patients. These ncRNAs represent promising new therapeutic targets for treating the disease and possibly as biomarkers for early diagnosis.

Acute myeloid leukemia (LAML) is one of the most prevalent hematological malignancies. In recent years, while targeted approaches have shown promise in the fight against cancer, the treatability and prognosis of patients remain inadequate due to the shortage of drugs. Noncoding RNAs, especially circular RNA (circRNA) and microRNA (miRNA), have been shown to play a unique role in tumor development. This study aims to identify the disease-associated circRNA–miRNA–mRNA network by bioinformatic analysis and investigate the mechanisms in the development and progression of LAML. Additionally, it reveals the promising roles of these molecules as a diagnostic biomarker and therapeutic target for LAML treatment. Using various bioinformatics approaches, we identified the hsa_circ_0058058/miR-324-5p axis in LAML and its possible functions in LAML development. According to our results, hsa circ-0058058 can regulate the expression of AP1G1 and SP1 through miR-324-5p to support angiogenesis, the cell cycle, and DNA replication processes. Downregulation of hsa circ-0058058 may contribute to the anticancer functions of miR-324-5p on LAML tumorigenesis, and upregulation of miR-324-5p can abolish the oncogenic effects of AP1G1 and SP1 on LAML tumorigenesis. Additionally, highly enriched pathways indicated possible interactions between molecules underlying LAML pathology. Targeted molecules within this network may be able to function as therapeutic and diagnostic biomarkers for disease, while more research and clinical confirmation are needed.

The development of childhood obesity is a complex process influenced by a combination of genetic predisposition and environmental factors, such as sleep, diet, physical activity, and socioeconomic status. Long-term solutions for decreasing the risk of childhood obesity remain elusive, despite significant advancements in promoting health and well-being in school and at home. Challenges persist in areas such as adherence to interventions, addressing underlying social determinants, and individual differences in response to treatment. Over the last decade, there has been significant progress in epigenetics, along with increased curiosity in gaining insights into how sleep and lifestyle decisions impact an individual’s health. Epigenetic modifications affect the expression of genes without causing changes to the fundamental DNA sequence. In recent years, numerous research studies have explored the correlation between sleep and the epigenome, giving a better understanding of DNA methylation, histone modification, and non-coding RNAs. Although significant findings have been made about the influence of sleep on epigenetics, a notable gap exists in the literature concerning sleep-related genes specifically associated with childhood obesity. Consequently, it is crucial to delve deeper into this area to enhance our understanding. Therefore, this review primarily focuses on the connection between sleep patterns and epigenetic modifications in genes related to childhood obesity. Exploring the interplay between sleep, epigenetics, and childhood obesity can potentially contribute to improved overall health outcomes. This comprehensive review encompasses studies focusing on sleep-related genes linked to obesity.

Abstract Across the world, oral cancer is a prevalent tumor. Over the years, both its mortality and incidence have grown. Oral cancer metastasis is a complex process involving cell invasion, migration, proliferation, and egress from cancer tissue either by lymphatic vessels or blood vessels. MicroRNAs (miRNAs) are essential short non-coding RNAs, which can act either as tumor suppressors or as oncogenes to control cancer development. Cancer metastasis is a multi-step process, in which miRNAs can inhibit or stimulate metastasis at all stages, including epithelial-mesenchymal transition, migration, invasion, and colonization, by targeting critical genes in these pathways. On the other hand, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), two different types of non-coding RNAs, can regulate cancer metastasis by affecting gene expression through cross-talk with miRNAs. We reviewed the scientific literature (Google Scholar, Scopus, and PubMed) for the period 2000–2023 to find reports concerning miRNAs and lncRNA/circRNA-miRNA-mRNA networks, which control the spread of oral cancer cells by affecting invasion, migration, and metastasis. According to these reports, miRNAs are involved in the regulation of metastasis pathways either by directly or indirectly targeting genes associated with metastasis. Moreover, circRNAs and lncRNAs can induce or suppress oral cancer metastasis by acting as competing endogenous RNAs to inhibit the effect of miRNA suppression on specific mRNAs. Overall, non-coding RNAs (especially miRNAs) could help to create innovative therapeutic methods for the control of oral cancer metastases.

Abstract Neurological disorders such as stroke, multiple sclerosis, as well as the neurodegenerative diseases Parkinson's or Alzheimer's disease are accompanied or even powered by danger associated molecular patterns (DAMPs), defined as endogenous molecules released from stressed or damaged tissue. Besides protein-related DAMPs or “alarmins”, numerous nucleic acid DAMPs exist in body fluids, such as cell-free nuclear and mitochondrial DNA as well as different species of extracellular RNA, collectively termed as self-extracellular nucleic acids (SENAs). Among these, microRNA, long non-coding RNAs, circular RNAs and extracellular ribosomal RNA constitute the majority of RNA-based DAMPs. Upon tissue injury, necrosis or apoptosis, such SENAs are released from neuronal, immune and other cells predominantly in association with extracellular vesicles and may be translocated to target cells where they can induce intracellular regulatory pathways in gene transcription and translation. The majority of SENA-induced signaling reactions in the brain appear to be related to neuroinflammatory processes, often causally associated with the onset or progression of the respective disease. In this review, the impact of the diverse types of SENAs on neuroinflammatory and neurodegenerative diseases will be discussed. Based on the accumulating knowledge in this field, several specific antagonistic approaches are presented that could serve as therapeutic interventions to lower the pathological outcome of the indicated brain disorders.

Abstract Background The interaction networks between coding and non-coding RNAs (ncRNAs) including long non-coding RNA (lncRNA), covalently closed circular RNA (circRNA) and miRNA are significant to elucidate molecular processes of biological activities and interactions between host and pathogen. Congenital infection caused by vertical transmission of microsporidia N. bombycis can result in severe economic losses in the silkworm-feeding industry. However, little is known about ncRNAs that take place in the microsporidia congenital infection. Here we conducted whole-transcriptome RNA-Seq analyses to identify ncRNAs and regulatory networks for both N. bombycis and host including silkworm embryos and larvae during the microsporidia congenital infection. Results A total of 4,171 mRNAs, 403 lncRNA, 62 circRNAs, and 284 miRNAs encoded by N. bombycis were identified, among which some differentially expressed genes formed cross-talk and are involved in N. bombycis proliferation and infection. For instance, a lncRNA/circRNA competing endogenous RNA (ceRNA) network including 18 lncRNAs, one circRNA, and 20 miRNAs was constructed to describe 14 key parasites genes regulation, such as polar tube protein 3 (PTP3), ricin-B-lectin, spore wall protein 4 (SWP4), and heat shock protein 90 (HSP90). Regarding host silkworm upon N. bombycis congenital infection, a total of 14,889 mRNAs, 3,038 lncRNAs, 19,039 circRNAs, and 3,413 miRNAs were predicted based on silkworm genome with many differentially expressed coding and non-coding genes during distinct developmental stages. Different species of RNAs form interacting network to modulate silkworm biological processes, such as growth, metamorphosis and immune responses. Furthermore, a lncRNA/circRNA ceRNA network consisting of 140 lncRNAs, five circRNA, and seven miRNAs are constructed hypothetically to describe eight key host genes regulation, such as Toll-6, Serpin-6, inducible nitric oxide synthase (iNOS) and Caspase-8. Notably, cross-species analyses indicate that parasite and host miRNAs play a vital role in pathogen-host interaction in the microsporidia congenital infection. Conclusion This is the first comprehensive pan-transcriptome study inclusive of both N. bombycis and its host silkworm with a specific focus on the microsporidia congenital infection, and show that ncRNA-mediated regulation plays a vital role in the microsporidia congenital infection, which provides a new insight into understanding the basic biology of microsporidia and pathogen-host interaction.

Abstract Reproductive traits play a vital role in determining the production efficiency of sheep. Maximizing the production is of paramount importance for breeders worldwide due to the growing population. Circular RNAs (circRNAs) act as miRNA sponges by absorbing miRNA activity through miRNA response elements (MREs) and participate in ceRNA regulatory networks (ceRNETs) to regulate mRNA expression. Despite of extensive research on role of circRNAs as miRNA sponges in various species, their specific regulatory roles and mechanism in sheep ovarian tissue are still not well understood. In this study, we performed whole genome sequencing of circRNAs, miRNA and mRNA employing bioinformatic techniques on ovine tissues of two contrasting sheep breeds "Small tail Han (X_LC) and Dolang sheep (D_LC)", which results into identification of 9,878 circRNAs with a total length of 23,522,667 nt and an average length of 2,381.32 nt. Among them, 44 differentially expressed circRNAs (DECs) were identified. Moreover, correlation between miRNA-mRNA and lncRNA-miRNA provided us with to prediction of miRNA binding sites on nine differentially expressed circRNAs and 165 differentially expressed mRNAs using miRanda. miRNA-mRNA and lncRNA-miRNA pairs with negative correlation were selected to determine the ceRNA score along with positively correlated pairs from lncRNA and mRNA network. Integration of ceRNA score and positively correlated pairs exhibit a significant ternary relationship among circRNAs-miRNA-mRNA demonestrated by ceRNA, comprising of 50 regulatory pairs sharring common nodes and predicted potential differentially expressed circRNAs-miRNAs-mRNAs regulatory axis. Based on functional enrichment analysis shortlisted key ceRNA regulatory pairs associated with reproduction including circRNA_3257-novel579_mature-EPHA3, circRNA_8396-novel130_mature-LOC101102473, circRNA_4140- novel34_mature > novel661_mature-KCNK9, and circRNA_8312-novel339_mature-LOC101110545. Furthermore, expression profiling, functional enrichments and qRT-PCR analysis of key target genes infer their implication in reproduction and metabolism. ceRNA target mRNAs evolutionary trajectories, expression profiling, functional enrichments, subcellular localizations following genomic organizations will provide new insights underlying molecular mechanisms of reproduction, and establish a solid foundation for future research. Graphical Abstract Graphical abstract summarizing the scheme of study

Jing Zhu,1,* Fei Huang,1,2,* Yonglin Hu,1,3,* Wei Qiao,1 Yingchao Guan,1 Zhi-Jun Zhang,1,* Su Liu,1 Ying Liu4 1Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, JiangSu Province, 226001, People’s Republic of China; 2Department of Rehabilitation Medicine, Nantong Health College of Jiangsu Province, Nantong, JiangSu Province, 226010, People’s Republic of China; 3Affiliated Nantong Rehabilitation Hospital of Nantong University, Nantong, JiangSu Province, 226001, People’s Republic of China; 4Department of Pathology, Affiliated Hospital of Nantong University, Nantong, JiangSu Province, 226001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Liu, Department of Pathology, Affiliated Hospital of Nantong University, Nantong, 226001, JiangSu Province, People’s Republic of China, Email proliuying@163.com Su Liu, Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Nantong, JiangSu Province, 226001, People’s Republic of China, Email 327202278@qq.comAbstract: Secondary chronic neuropathic pain (NP) in addition to sensory, motor, or autonomic dysfunction can significantly reduce quality of life after spinal cord injury (SCI). The mechanisms of SCI-related NP have been studied in clinical trials and with the use of experimental models. However, in developing new treatment strategies for SCI patients, NP poses new challenges. The inflammatory response following SCI promotes the development of NP. Previous studies suggest that reducing neuroinflammation following SCI can improve NP-related behaviors. Intensive studies of the roles of non-coding RNAs in SCI have discovered that ncRNAs bind target mRNA, act between activated glia, neuronal cells, or other immunocytes, regulate gene expression, inhibit inflammation, and influence the prognosis of NP.Keywords: non‐coding RNAs, neuroinflammation, neuropathic pain, spinal cord injury

Bronchial asthma, commonly known as asthma, is a chronic inflammatory disease characterized by airway inflammation, increased responsiveness and changes in airway structure. T cells, particularly T helper cells, play a crucial role in the disease. Non-coding RNAs, which are RNAs that do not code for proteins, mainly include microRNAs, long non-coding RNAs, and circular RNAs, play a role in regulating various biological processes. Studies have shown that non-coding RNAs have an important role in the activation and transformation of T cells and other biological processes in asthma. The specific mechanisms and clinical applications are worth further examination. This article reviews the recent research on the role of microRNAs, long non-coding RNAs and circular RNAs in T cells in asthma.

Diabetes mellitus (DM) is a first-line priority among the problems facing medical science and public health in almost all countries of the world. The main problem of DM is the high incidence of damage to the cardiovascular system, which in turn leads to diseases such as myocardial infarction, stroke, gangrene of the lower extremities, blindness and chronic renal failure. As a result, the study of the molecular genetic mechanisms of the pathogenesis of DM is of critical importance for the development of new diagnostic and therapeutic strategies. Molecular genetic aspects of the etiology and pathogenesis of diabetes mellitus are intensively studied in well-known laboratories around the world. One of the strategies in this direction is to study the role of exosomes in the pathogenesis of DM. Exosomes are microscopic extracellular vesicles with a diameter of 30–100 nm, released into the intercellular space by cells of various tissues and organs. The content of exosomes depends on the cell type and includes mRNA, non-coding RNAs, DNA, and so on. Non-coding RNAs, a group of RNAs with limited transcriptional activity, have been discovered to play a significant role in regulating gene expression through epigenetic and posttranscriptional modulation, such as silencing of messenger RNA. One of the problems of usage exosomes in DM is the identification of the cellular origin of exosomes and the standardization of protocols for molecular genetic studies in clinical laboratories. In addition, the question of the target orientation of exosomes and their targeted activity requires additional study. Solving these and other problems will make it possible to use exosomes for the diagnosis and delivery of drugs directly to target cells in DM. This study presents an analysis of literature data on the role of exosomes and ncRNAs in the development and progression of DM, as well as the prospects for the use of exosomes in clinical practice in this disease.

Objectives: Summarize the progress and hot topic evolution of non-coding RNAs (ncRNAs) research in esophageal squamous cell carcinoma (ESCC) in recent years and predict future research directions.Methods: Relevant articles from the Web of Science until 31 October 2023 were obtained. Bibliometric analysis of included articles was performed using software (VOSviewer, CiteSpace, and Bibliometrix). The volume and citation of publications, as well as the country, institution, author, journal, keywords of the articles were used as variables to analyze the research trends and hot spot evolution.Results: 1,118 literature from 2008 to 2023 were retrieved from database, with 25 countries/regions, 793 institutions, 5,426 authors, 261 journals involved. Global cooperation was centered on China, Japan, and the United States. Zhengzhou University, an institution from China, had the highest publication. The most prolific author was Guo Wei, and the most prolific journal was Oncology Letters. Analysis of keywords revealed that the research in this field revolved around the role of ncRNAs in the occurrence, development, diagnosis, treatment, and prognosis of ESCC, mainly including micro RNAs, long non-coding RNAs, and then circular RNAs.Conclusion: Overall, research on ncRNAs in ESCC remains strong. Previous research has mainly focused on the basic research, with a focus on the mechanism of ncRNAs in the occurrence, development, diagnosis, treatment, and prognosis of ESCC. Combining current research with emerging disciplines to further explore its mechanisms of action or shifting the focus of research from preclinical research to clinical research based on diagnosis, treatment, and prognosis, will be the main breakthrough in this field in the future.

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes, and hyperglycemic memory associated with diabetes carries the risk of disease occurrence, even after the termination of blood glucose injury. The existence of hyperglycemic memory supports the concept of an epigenetic mechanism involving n6-methyladenosine (m6A) modification. Several studies have shown that m6A plays a key role in the pathogenesis of DKD. This review addresses the role and mechanism of m6A RNA modification in the progression of DKD, including the regulatory role of m6A modification in pathological processes, such as inflammation, oxidative stress, fibrosis, and non-coding (nc) RNA. This reveals the importance of m6A in the occurrence and development of DKD, suggesting that m6A may play a role in hyperglycemic memory phenomenon. This review also discusses how some gray areas, such as m6A modified multiple enzymes, interact to affect the development of DKD and provides countermeasures. In conclusion, this review enhances our understanding of DKD from the perspective of m6A modifications and provides new targets for future therapeutic strategies. In addition, the insights discussed here support the existence of hyperglycemic memory effects in DKD, which may have far-reaching implications for the development of novel treatments. We hypothesize that m6A RNA modification, as a key factor regulating the development of DKD, provides a new perspective for the in-depth exploration of DKD and provides a novel option for the clinical management of patients with DKD.

Alzheimer’s disease (AD) is a complex, multifactorial disorder, influenced by a multitude of variables ranging from genetic factors, age, and head injuries to vascular diseases, infections, and various other environmental and demographic determinants. Among the environmental factors, the role of the microbiome in the genesis of neurodegenerative disorders (NDs) is gaining increased recognition. This paradigm shift is substantiated by an extensive body of scientific literature, which underscores the significant contributions of microorganisms, encompassing viruses and gut-derived bacteria, to the pathogenesis of AD. The mechanism by which microbial infection exerts its influence on AD hinges primarily on inflammation. Neuroinflammation, activated in response to microbial infections, acts as a defense mechanism for the brain but can inadvertently lead to unexpected neuropathological perturbations, ultimately contributing to NDs. Given the ongoing uncertainty surrounding the genetic factors underpinning ND, comprehensive investigations into environmental factors, particularly the microbiome and viral agents, are imperative. Recent advances in neuroscientific research have unveiled the pivotal role of non-coding RNAs (ncRNAs) in orchestrating various pathways integral to neurodegenerative pathologies. While the upstream regulators governing the pathological manifestations of microorganisms remain elusive, an in-depth exploration of the nuanced role of ncRNAs holds promise for the development of prospective therapeutic interventions. This review aims to elucidate the pivotal role of ncRNAs as master modulators in the realm of neurodegenerative conditions, with a specific focus on Alzheimer’s disease.

The burden of lung diseases is gradually increasing with an increase in the average human life expectancy. Therefore, it is necessary to identify effective methods to treat lung diseases and reduce their social burden. Currently, an increasing number of studies focus on the role of mesenchymal stem cell-derived exosomes (MSC-Exos) as a cell-free therapy in lung diseases. They show great potential for application to lung diseases as a more stable and safer option than traditional cell therapies. MSC-Exos are rich in various substances, including proteins, nucleic acids, and DNA. Delivery of Non-coding RNAs (ncRNAs) enables MSC-Exos to communicate with target cells. MSC-Exos significantly inhibit inflammatory factors, reduce oxidative stress, promote normal lung cell proliferation, and reduce apoptosis by delivering ncRNAs. Moreover, MSC-Exos carrying specific ncRNAs affect the proliferation, invasion, and migration of lung cancer cells, thereby playing a role in managing lung cancer. The detailed mechanisms of MSC-Exos in the clinical treatment of lung disease were explored by developing standardized culture, isolation, purification, and administration strategies. In summary, MSC-Exo-based delivery methods have important application prospects for treating lung diseases.

Ulcerative colitis (UC) is an inflammatory bowel disease, and is characterized by the diffuse inflammation and ulceration in the colon and rectum mucosa, even extending to the caecum. Epigenetic modifications, including DNA methylations, histone modifications and non-coding RNAs, are implicated in the differentiation, maturation, and functional modulation of multiple immune and non-immune cell types, and are influenced and altered in various chronic inflammatory diseases, including UC. Here we review the relevant studies revealing the differential epigenetic features in UC, and summarize the current knowledge about the immunopathogenesis of UC through epigenetic regulation and inflammatory signaling networks, regarding DNA methylation, histone modification, miRNAs and lncRNAs. We also discuss the epigenetic-associated therapeutic strategies for the alleviation and treatment of UC, which will provide insights to intervene in the immunopathological process of UC in view of epigenetic regulation.

BackgroundTo investigate the correlation between lg (circSCMH1/miR-874) and acute coronary syndrome (ACS), acute myocardial infarction (AMI), and carotid plaque stability.Methods701 patients were divided into stable coronary artery disease (SCAD), ACS, and control groups. Furthermore, 225 patients who underwent carotid ultrasound were selected from the above 701 patients and were divided into low-risk plaque, medium-to-high risk plaque, and control (without carotid plaques) groups. We collected their baseline characteristics and measured the contents of exosomal circSCMH1 and miR-874 in peripheral blood. Then lg(circSCMH1/miR-874) was calculated and statistical analysis was performed.ResultsThe lg (circSCMH1/miR-874) values of ACS, SCAD, and the control group decreased successively (P

Hemoglobin switching is a complex biological process not yet fully elucidated. The mechanism regulating the suppression of fetal hemoglobin (HbF) expression is of particular interest because of the positive impact of HbF on the course of diseases such as β-thalassemia and sickle cell disease, hereditary hemoglobin disorders that affect the health of countless individuals worldwide. Several transcription factors have been implicated in the control of HbF, of which BCL11A has emerged as a major player in HbF silencing. SOX6 has also been implicated in silencing HbF and is critical to the silencing of the mouse embryonic hemoglobins. BCL11A and SOX6 are co-expressed and physically interact in the erythroid compartment during differentiation. In this study, we observe that BCL11A knockout leads to post-transcriptional downregulation of SOX6 through activation of microRNA (miR)-365-3p. Downregulating SOX6 by transient ectopic expression of miR-365-3p or gene editing activates embryonic and fetal β-like globin gene expression in erythroid cells. The synchronized expression of BCL11A and SOX6 is crucial for hemoglobin switching. In this study, we identified a BCL11A/miR-365-3p/SOX6 evolutionarily conserved pathway, providing insights into the regulation of the embryonic and fetal globin genes suggesting new targets for treating β-hemoglobinopathies.

Atherosclerosis is the leading cause of numerous cardiovascular diseases with a high mortality rate. Non-coding RNAs (ncRNAs), RNA molecules that do not encode proteins in human genome transcripts, are known to play crucial roles in various physiological and pathological processes. Recently, researches on the regulation of atherosclerosis by ncRNAs, mainly including microRNAs, long noncoding RNAs, and circular RNAs, have gradually become a hot topic. Traditional Chinese medicine has been proved to be effective in treating cardiovascular diseases in China for a long time, and its active monomers have been found to target a variety of atherosclerosis-related ncRNAs. These active monomers of traditional Chinese medicine hold great potential as drugs for the treatment of atherosclerosis. Here, we summarized current advancement of the molecular pathways by which ncRNAs regulate atherosclerosis and mainly highlighted the mechanisms of traditional Chinese medicine monomers in regulating atherosclerosis through targeting ncRNAs. [ABSTRACT FROM AUTHOR]

Duck meat is pivotal in providing high-quality protein for human nutrition, underscoring the importance of studying duck myogenesis. The regulatory mechanisms governing duck myogenesis involve both coding and non-coding RNAs, yet their specific expression patterns and molecular mechanisms remain elusive. To address this knowledge gap, we performed expression profiling analyses of mRNAs, lncRNAs, circRNAs, and miRNAs involved in duck myogenesis using whole-transcriptome RNA-seq. Our analysis identified 1733 differentially expressed (DE)-mRNAs, 1116 DE-lncRNAs, 54 DE-circRNAs, and 174 DE-miRNAs when comparing myoblasts and myotubes. A GO analysis highlighted the enrichment of DE molecules in the extracellular region, protein binding, and exocyst. A KEGG analysis pinpointed pathways related to ferroptosis, PPAR signaling, nitrogen metabolism, cell cycle, cardiac muscle contraction, glycerolipid metabolism, and actin cytoskeleton. A total of 51 trans-acting lncRNAs, including ENSAPLT00020002101 and ENSAPLT00020012069, were predicted to participate in regulating myoblast proliferation and differentiation. Based on the ceRNAs, we constructed lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA ceRNA networks involving five miRNAs (miR-129-5p, miR-133a-5p, miR-22-3p, miR-27b-3p, and let-7b-5p) that are relevant to myogenesis. Furthermore, the GO and KEGG analyses of the DE-mRNAs within the ceRNA network underscored the significant enrichment of the glycerolipid metabolism pathway. We identified five different DE-mRNAs, specifically ENSAPLG00020001677, ENSAPLG00020002183, ENSAPLG00020005019, ENSAPLG00020010497, and ENSAPLG00020017682, as potential target genes that are crucial for myogenesis in the context of glycerolipid metabolism. These five mRNAs are integral to ceRNA networks, with miR-107_R-2 and miR-1260 emerging as key regulators. In summary, this study provides a valuable resource elucidating the intricate interplay of mRNA-lncRNA-circRNA-miRNA in duck myogenesis, shedding light on the molecular mechanisms that govern this critical biological process. [ABSTRACT FROM AUTHOR]

Non-coding RNAs (ncRNAs) are abundant single-stranded RNA molecules in human cells, involved in various cellular processes ranging from DNA replication and mRNA translation regulation to genome stability defense. MicroRNAs are multifunctional ncRNA molecules of 18–24 nt in length, involved in gene silencing through base-pair complementary binding to target mRNA transcripts. piwi-interacting RNAs are an animal-specific class of small ncRNAs sized 26–31 nt, responsible for the defense of genome stability via the epigenetic and post-transcriptional silencing of transposable elements. Long non-coding RNAs are ncRNA molecules defined as transcripts of more than 200 nucleotides, their function depending on localization, and varying from the regulation of cell differentiation and development to the regulation of telomere-specific heterochromatin modifications. The current review provides recent data on the several forms of small and long non-coding RNA's potential to act as diagnostic, prognostic or therapeutic target for various human diseases. [ABSTRACT FROM AUTHOR]

Female common carp grow faster than male individuals, implying that rearing females could be more profitable in aquaculture. Non-coding RNAs (ncRNAs) serve as versatile regulators with multiple functions in diverse biological processes. However, the roles of ncRNAs in the sex differentiation of common carp are less studied. In this study, we investigated the expression profiles of ncRNAs, including miRNAs, lncRNAs, and circRNAs, in the gonads to comprehend the roles of ncRNAs in sex differentiation in common carp. A substantial number of differentially expressed (DE) ncRNAs in ovaries and testes were identified. Some miRNAs, notably miR-205, miR-214, and miR-460-5p, might modulate hormone synthesis and thus maintain sex. A novel miRNA, novel_158, was predicted to suppress the expression of foxl3. DE lncRNAs were associated with oocyte meiosis, GnRH signaling pathways, and steroid biosynthesis, while DE circRNA target genes were enriched in the WNT signaling pathway and MAPK signaling pathway. We also analyzed ncRNA-mRNA interactions to shed light on the crosstalk between competing endogenous RNAs (ceRNAs), which is the critical mechanism by which lncRNAs and circRNAs function. Some lncRNAs and circRNAs may be able to competitively bind novel_313, a new miRNA, and thus regulate hsd17β3. Our research will provide a valuable resource for understanding the genetic basis of gonadal differentiation and development in common carp. [ABSTRACT FROM AUTHOR]

Plant senescence is the last stage of plant development and a type of programmed cell death, occurring at a predictable time and cell. It involves the functional conversion from nutrient assimilation to nutrient remobilization, which substantially impacts plant architecture and plant biomass, crop quality, and horticultural ornamental traits. In past two decades, DNA damage was believed to be a main reason for cell senescence. Increasing evidence suggests that the alteration of epigenetic information is a contributing factor to cell senescence in organisms. In this review, we summarize the current research progresses of epigenetic and epitranscriptional mechanism involved in cell senescence of plant, at the regulatory level of DNA methylation, histone methylation and acetylation, chromatin remodeling, non-coding RNAs and RNA methylation. Furthermore, we discuss their molecular genetic manipulation and potential application in agriculture for crop improvement. Finally we point out the prospects of future research topics. [ABSTRACT FROM AUTHOR]

An unique subclass of functional non-coding RNAs generated by transfer RNA (tRNA) under stress circumstances is known as tRNA-derived small RNA (tsRNA). tsRNAs can be divided into tRNA halves and tRNA-derived fragments (tRFs) based on the different cleavage sites. Like microRNAs, tsRNAs can attach to Argonaute (AGO) proteins to target downstream mRNA in a base pairing manner, which plays a role in rRNA processing, gene silencing, protein expression and viral infection. Notably, tsRNAs can also directly bind to protein and exhibit functions in transcription, protein modification, gene expression, protein stabilization, and signaling pathways. tsRNAs can control the expression of tumor suppressor genes and participate in the initiation of cancer. It can also mediate the progression of diseases by regulating cell viability, migration ability, inflammatory factor content and autophagy ability. Precision medicine targeting tsRNAs and drug therapy of plant-derived tsRNAs are expected to be used in clinical practice. In addition, liquid biopsy technology based on tsRNAs indicates a new direction for the non-invasive diagnosis of diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Given the increasing incidence of hepatocellular carcinoma (HCC) worldwide, a full comprehension of the molecular pathways supporting HCC onset and progression is urgently needed to design more tailored prognostic models and appropriate therapeutic approaches. A large number of pro-carcinogenic and anti-carcinogenic mechanisms are regulated by RNA non-coding transcripts known as non-coding RNAs (ncRNAs). This review reports the main dysregulated ncRNAs involved in HCC cancerogenesis and describes the relative implications on the progression mechanisms highlighting potential markers for the early diagnosis of HCC and targets for innovative therapeutic strategies. Hepatocellular carcinoma (HCC) is a predominant malignancy with increasing incidences and mortalities worldwide. In Western countries, the progressive affirmation of Non-alcoholic Fatty Liver Disease (NAFLD) as the main chronic liver disorder in which HCC occurrence is appreciable even in non-cirrhotic stages, constitutes a real health emergency. In light of this, a further comprehension of molecular pathways supporting HCC onset and progression represents a current research challenge to achieve more tailored prognostic models and appropriate therapeutic approaches. RNA non-coding transcripts (ncRNAs) are involved in the regulation of several cancer-related processes, including HCC. When dysregulated, these molecules, conventionally classified as "small ncRNAs" (sncRNAs) and "long ncRNAs" (lncRNAs) have been reported to markedly influence HCC-related progression mechanisms. In this review, we describe the main dysregulated ncRNAs and the relative molecular pathways involved in HCC progression, analyzing their implications in certain etiologically related contexts, and their applicability in clinical practice as novel diagnostic, prognostic, and therapeutic tools. Finally, given the growing evidence supporting the immune system response, the oxidative stress-regulated mechanisms, and the gut microbiota composition as relevant emerging elements mutually influencing liver-cancerogenesis processes, we investigate the relationship of ncRNAs with this triad, shedding light on novel pathogenetic frontiers of HCC progression. [ABSTRACT FROM AUTHOR]

Cancer metastasis is one of the major clinical challenges worldwide due to limited existing effective treatments. Metastasis roots from the host organ of origin and gradually migrates to different regional and distant organs. In different breast cancer subtypes, different organs like bones, liver, lungs and brain are targeted by the metastatic tumor cells. Cancer renders mortality to their respective metastasizing sites like bones, brain, liver, and lungs. Metastatic breast cancers are best treated and managed if detected at an early stage. Metastasis is regulated by various molecular activators and suppressors. The conventional theory of 'seed and soil' states that metastatic tumor cells move to tumor microenvironment that has favorable conditions like blood flow for them to grow just like seeds grows when planted in fertile land. Additionally, different coding as well as non-coding RNAs play a very significant role in the process of metastasis by modulating their expression levels leading to a crosstalk of various tumorigenic cascades. Treatments for metastasis is also very critical in controlling this lethal process. Detecting breast cancer metastasis at an early stage is crucial for managing and predicting metastatic progression. In this review, we have compiled several factors that can be targeted to manage the onset and gradual stages of breast cancer metastasis. [ABSTRACT FROM AUTHOR]

Trigeminal neuropathic pain (TNP) induces mechanical allodynia and hyperalgesia, which are known to alter gene expression in injured dorsal root ganglia primary sensory neurons. Non-coding RNAs (ncRNAs) have been linked to TNP. However, the functional mechanism underlying TNP and the expression profile of ncRNAs in the trigeminal ganglion (TG) and trigeminal subnucleus caudalis (Sp5C) are still unknown. We used RNA sequencing and bioinformatics analysis to examine the TG and Sp5C transcriptomes after infraorbital nerve chronic constrictive injury (IoN-CCI). The robust changes in the gene expression of lncRNAs, circRNAs, and mRNAs were observed within the TG and Sp5C from mice that underwent IoNCCI and the sham-operated mice (day 7). In total, 111,003 lncRNAs were found in TG and 107,157 in Sp5C; 369 lncRNAs were differentially expressed in TG, and 279 lncRNAs were differentially expressed in Sp5C. In addition, 13,216 circRNAs in TG and 21,658 circRNAs in Sp5C were identified, with 1,155 circRNAs and 2,097 circRNAs differentially expressed in TG and Sp5C, respectively. Furthermore, 5,205 DE mRNAs in TG and 3,934 DE mRNAs in Sp5C were differentially expressed between IoN-CCI and sham groups. The study revealed a high correlation of pain-related differentially expressed genes in the TG and Sp5C to anxiety, depression, inflammation, neuroinflammation, and apoptosis. Gene Ontology analysis revealed that binding-related molecular functions and membrane-related cell components were significantly enriched. Kyoto Encyclopedia of Genes and Genomes analysis shows the most significant enrichments in neurogenesis, nervous system development, neuron differentiation, adrenergic signaling, cAMP signaling, MAPK signaling, and PI3KAkt signaling pathways. Furthermore, protein-protein interaction analysis showed that hub genes were implicated in neuropeptide signaling pathways. Functional analysis of DE ncRNA-targeting genes was mostly enriched with nociceptionrelated signaling pathways underpinning TNP. Our findings suggest that ncRNAs are involved in TNP development and open new avenues for research and treatment. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC), characterized by high invasiveness, is associated with poor prognosis and elevated mortality rates. Despite the development of effective therapeutic targets for TNBC, systemic chemotherapy and radiotherapy (RdT) remain prevalent treatment modalities. One notable challenge of RdT is the acquisition of radioresistance, which poses a significant obstacle in achieving optimal treatment response. Compelling evidence implicates non-coding RNAs (ncRNAs), gene expression regulators, in the development of radioresistance. This systematic review focuses on describing the role, association, and/or involvement of ncRNAs in modulating radioresponse in TNBC. In adhrence to the PRISMA guidelines, an extensive and comprehensive search was conducted across four databases using carefully selected entry terms. Following the evaluation of the studies based on predefined inclusion and exclusion criteria, a refined selection of 37 original research articles published up to October 2023 was obtained. In total, 33 different ncRNAs, including lncRNAs, miRNAs, and circRNAs, were identified to be associated with radiation response impacting diverse molecular mechanisms, primarily the regulation of cell death and DNA damage repair. The findings highlighted in this review demonstrate the critical roles and the intricate network of ncRNAs that significantly modulates TNBC's responsiveness to radiation. The understanding of these underlying mechanisms offers potential for the early identification of non-responders and patients prone to radioresistance during RdT, ultimately improving TNBC survival outcomes. [ABSTRACT FROM AUTHOR]

Osteomyelitis is a debilitating bone infection primarily caused by Staphylococcus aureus. Despite advancements in surgery and chemotherapy, the treatment of osteomyelitis remains unsatisfactory, characterized by antibiotic resistance and recurrent relapses. Numerous studies have confirmed that non-coding RNAs could play an emerging role in regulating gene expression, as well as in the differentiation of osteoblasts and osteoclasts, along with bone formation. In this context, we provide an overview of current knowledge regarding the roles of non-coding RNAs in osteomyelitis and explore the potential therapeutic applications of these molecules in disease management, aiming to uncover novel diagnostic and treatment approaches. [ABSTRACT FROM AUTHOR]

Sugar beet is susceptible to Beet curly top virus (BCTV), which significantly reduces yield and sugar production in the semi-arid growing regions worldwide. Sources of genetic resistance to BCTV is limited and control depends upon insecticide seed treatments with neonicotinoids. Through double haploid production and genetic selection, BCTV resistant breeding lines have been developed. Using BCTV resistant (R) [KDH13; Line 13 and KDH4-9; Line 4] and susceptible (S) [KDH19-17; Line 19] lines, beet leafhopper mediated natural infection, mRNA/sRNA sequencing, and metabolite analyses, potential mechanisms of resistance against the virus and vector were identified. At early infection stages (2- and 6-days post inoculation), examples of differentially expressed genes highly up-regulated in the 'R' lines (vs. 'S') included EL10Ac5g10437 (inhibitor of trypsin and hageman factor), EL10Ac6g14635 (jasmonate-induced protein), EL10Ac3g06016 (ribosome related), EL10Ac2g02812 (probable prolyl 4-hydroxylase 10), etc. Pathway enrichment analysis showed differentially expressed genes were predominantly involved with peroxisome, amino acids metabolism, fatty acid degradation, amino/nucleotide sugar metabolism, etc. Metabolite analysis revealed significantly higher amounts of specific isoflavonoid O-glycosides, flavonoid 8-C glycosides, triterpenoid, and iridoid-O-glycosides in the leaves of the 'R' lines (vs. 'S'). These data suggest that a combination of transcriptional regulation and production of putative antiviral metabolites might contribute to BCTV resistance. In addition, genome divergence among BCTV strains differentially affects the production of small non-coding RNAs (sncRNAs) and small peptides which may potentially affect pathogenicity and disease symptom development. [ABSTRACT FROM AUTHOR]

Cardiovascular aging has been reported to accelerate in spaceflights, which is a great potential risk to astronauts' health and performance. However, current exercise routines are not sufficient to reverse the adverse effects of microgravity exposure. Recently, salidroside (SAL), a valuable medicinal herb, has been demonstrated to display an important role for prevention and treatment in cardiovascular and other diseases. In the present work, Sprague–Dawley rats with four-week tail-suspension hindlimb-unloading were used to simulate microgravity effects on the cardiovascular system. We found that intragastrical administration of SAL not only significantly decreased the expressions of senescence biomarkers, such as P65 and P16, but also obviously increased the expressions of BK-dependent apoptotic genes, including the large-conductance calcium-activated K+ channel (BK), Bax, Bcl-2, and cleaved caspase-3, in vascular smooth muscle cells (VSMCs) in vivo and in vitro. In addition, relative non-coding RNAs were screened, and a luciferase assay identified that SAL increased apoptosis by activating LncRNA-FLORPAR, inhibiting miR-193, and then triggering the activity of the BK-α subunit. Our work indicated that SAL is a novel non-coding RNA modulator for regulating the LncRNA-FLORPAR sponging miR-193 pathway, which significantly promoted BK-dependent apoptosis and delayed cerebrovascular aging-like remodeling during simulated microgravity exposure. Our findings may provide a new approach to prevent cardiovascular aging in future spaceflights. [ABSTRACT FROM AUTHOR]

Head and neck cancers (HNC) encompass a broad spectrum of neoplastic disorders characterized by significant morbidity and mortality. While contemporary therapeutic interventions offer promise, challenges persist due to tumor recurrence and metastasis. Central to HNC pathogenesis is the aberration in numerous signaling cascades. Prominently, the Wnt signaling pathway has been critically implicated in the etiology of HNC, as supported by a plethora of research. Equally important, variations in the expression of non-coding RNAs (ncRNAs) have been identified to modulate key cancer phenotypes such as cellular proliferation, epithelial-mesenchymal transition, metastatic potential, recurrence, and treatment resistance. This review aims to provide an exhaustive insight into the multifaceted influence of ncRNAs on HNC, with specific emphasis on their interactions with the Wnt/β-catenin (WBC) signaling axis. We further delineate the effect of ncRNAs in either exacerbating or attenuating HNC progression via interference with WBC signaling. An overview of the mechanisms underlying the interplay between ncRNAs and WBC signaling is also presented. In addition, we described the potential of various ncRNAs in enhancing the efficacy of chemotherapeutic and radiotherapeutic modalities. In summary, this assessment posits the potential of ncRNAs as therapeutic agents targeting the WBC signaling pathway in HNC management. [ABSTRACT FROM AUTHOR]

Non-coding RNAs (ncRNAs) are a group of molecules critical for cell development and growth regulation. They are key regulators of important cellular pathways in the tumor microenvironment. To analyze ncRNAs in the tumor microenvironment, the use of RNA sequencing technology has revolutionized the field. The advancement of this technique has broadened our understanding of the molecular biology of cancer, presenting abundant possibilities for the exploration of novel biomarkers for cancer treatment. In this review, we will summarize recent achievements in understanding the complex role of ncRNA in the tumor microenvironment, we will report the latest studies on the tumor microenvironment using RNA sequencing, and we will discuss the potential use of ncRNAs as therapeutics for the treatment of cancer. [ABSTRACT FROM AUTHOR]