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Mitochondria are central to cellular function, particularly in metabolically active tissues such as skeletal muscle. Nuclear-encoded RNAs typically localize within the nucleus and cytosol but a small population may also translocate to subcellular compartments such as mitochondria. We aimed to investigate the nuclear-encoded RNAs that localize within the mitochondria of skeletal muscle cells and tissue. Intact mitochondria were isolated via immunoprecipitation (IP) followed by enzymatic treatments (RNase-A and proteinase-K) optimized to remove transcripts located exterior to mitochondria, making it amenable for high-throughput transcriptomic sequencing. Small RNA sequencing libraries were successfully constructed from as little as 1.8 ng mitochondrial RNA input. Small RNA sequencing of mitochondria from rat myoblasts revealed the enrichment of over 200 miRNAs. Whole-transcriptome RNA sequencing of enzymatically purified mitochondria isolated by IP from skeletal muscle tissue showed a striking similarity in the degree of purity compared to mitoplast preparations which lack an outer mitochondrial membrane. In summary, we describe a novel, powerful sequencing approach applicable to animal and human tissues and cells that can facilitate the discovery of nuclear-encoded RNA transcripts localized within skeletal muscle mitochondria., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in diabetes mellitus. It is also a significant contributor to cardiovascular morbidity and mortality in diabetic patients Thereby, Innovative therapeutic approaches are needed to retard the initiation and advancement of DN. Hyperglycemia can induce apoptosis, a regulated form of cell death, in multiple renal cell types, such as podocytes, mesangial cells, and proximal tubule epithelial cells, ultimately contributing to the pathogenesis of DN. Recent genome-wide investigations have revealed the widespread transcription of the human genome, resulting in the production of numerous regulatory non-protein-coding RNAs (ncRNAs), including microRNAs (miRNAs) and diverse categories of long non-coding RNAs (lncRNAs). They play a critical role in preserving physiological homeostasis, while their dysregulation has been implicated in a broad spectrum of disorders, including DN. Considering the established association between apoptotic processes and the expression of ncRNAs in DN, a thorough understanding of their intricate interplay is essential. Therefore, the current work thoroughly analyzes the intricate interplay among miRNAs, lncRNAs, and circular RNAs in the context of apoptosis within the pathogenesis of DN. Additionally, in the final section, we demonstrated that ncRNA-mediated modulation of apoptosis can be achieved through stem cell-derived exosomes and herbal medicines, presenting potential avenues for the treatment of DN., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Osteosarcoma (OS) represents the primary form of bone cancer observed in paediatric and adolescent populations. Nearly 10%-15% of patients have metastases at diagnosis, and the 5-year survival rate was less than 20%. Although numerous investigators have offered significant efforts, the survival rates for patients with OS have remained almost unchanged over the past three decades. The most pervasive and abundant modification of internal transcripts in eukaryotic messenger RNAs (mRNAs) is N6-methyladenosine (m6A), and it is regulated by m6A methylation regulators. A number of recent studies have demonstrated that m6A modifications can regulate the biological activities of tumour cells and are intimately linked with cancer development, prognosis, drug resistance, and therapy. N6-methyladenosine modification of Non-coding RNA (ncRNA) has likewise shown a broad potential in gene regulation and tumor biology. Epigenetic changes induced by mRNAs and ncRNAs methylation are important for a better understanding of OS development and targeted drug development. Therefore, this paper summarises the biological functions of m6A-modified regulators in osteosarcoma and the role of mutual regulation between m6A and ncRNAs in osteosarcoma. Furthermore, the potential clinical applications of m6A modifications in OS are presented for consideration. It provides new directions for the future research and clinical treatment strategies of osteosarcoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Plant genomes, through their evolutionary journey, have developed a complex composition that includes not only protein-coding sequences but also a significant amount of non-coding DNA, repetitive sequences, and transposable elements, traditionally labeled as "junk DNA". RNA molecules from these regions, labeled as "transcriptional junk," include non-coding RNAs, alternatively spliced transcripts, untranslated regions (UTRs), and short open reading frames (sORFs). However, recent research shows that this genetic material plays crucial roles in gene regulation, affecting plant growth, development, hormonal balance, and responses to stresses. Additionally, some of these regulatory regions encode small proteins, such as miRNA-encoded peptides (miPEPs) and microProteins (miPs), which interact with DNA or nuclear proteins, leading to chromatin remodeling and modulation of gene expression. This review aims to consolidate our understanding of the diverse roles that these so-called "transcriptional junk" regions play in regulating various physiological processes in plants., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Fibrosis is a process involving excessive accumulation of extracellular matrix components, the severity of which interferes with the function of the organ in question. With the advances in RNA sequencing and in-depth molecular studies, a large number of current studies have pointed out the irreplaceable role of non-coding RNAs (ncRNAs) in the pathophysiological development of organ fibrosis. Here, by summarizing the results of a large number of studies on the interactions between ncRNAs, some studies have found that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), among others, are able to act as sponges or decoy decoys for microRNAs (miRNAs), act as competing endogenous RNAs (ceRNAs) to regulate the expression of miRNAs, and subsequently act on different mRNA targets, playing a role in the development of fibrosis in a wide variety of organs, including the heart, liver, kidneys, and spleen. parenchymal organs, including heart, liver, kidney, and spleen, play important roles in the development of fibrosis. These findings elucidate the intricate involvement of the lncRNA/circRNA-miRNA-mRNA axis in the pathophysiological processes underpinning organ fibrosis, thereby enhancing our comprehension of the onset and progression of this condition. Furthermore, they introduce novel potential therapeutic targets within the realm of ncRNA-based therapeutics, offering avenues for the development of innovative drugs aimed at mitigating or reversing the effects of organ fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. None, (Copyright © 2024. Published by Elsevier Inc.)

Over the past decade, regulatory non-coding RNAs (ncRNAs) produced by RNA Pol II have been revealed as meaningful players in various essential cellular functions. In particular, thousands of ncRNAs are produced at transcriptional regulatory elements such as enhancers and promoters, where they may exert multiple functions to regulate proper development, cellular programming, transcription or genomic stability. Here, we review the mechanisms involving these regulatory element-associated ncRNAs, and particularly enhancer RNAs (eRNAs) and PROMoter uPstream Transcripts (PROMPTs). We contextualize the mechanisms described to the processing and degradation of these short lived RNAs. We summarize recent findings explaining how ncRNAs operate locally at promoters and enhancers, or further away, either shortly after their production by RNA Pol II, or through post-transcriptional stabilization. Such discoveries lead to a converging model accounting for how ncRNAs influence cellular fate, by acting on transcription and chromatin structure, which may further involve factors participating to 3D nuclear organization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

This study aims to elucidate the key regulatory molecules, specifically messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and microRNAs (miRNAs) and their roles in the development and progression of spinal cord injury (SCI). Expression profiles (GSE45006, GSE19890, and GSE125630) for SCI were sourced from the Gene Expression Omnibus (GEO) database. By comparing rats with SCI at various time points against those without SCI, we identified differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs), and miRNAs (DEmiRNAs). The GSE45006 dataset facilitated the production of DEmRNAs, which were then clustered using Mfuzz. Subsequently, we constructed a protein-protein interaction (PPI) network and anticipated interaction pairs between miRNA-mRNA and lncRNA-mRNA. These pairs were instrumental in forming a regulatory network involving lncRNA-miRNA-mRNA interactions. Additionally, we conducted functional enrichment studies on the DEmRNAs within these gene networks. A total of 2313 DEmRNAs were identified using the GSE45006 dataset, alongside 111 DEmiRNAs from GSE19890. From GSE125630, we extracted 154 DElncRNAs and 2322 DEmRNAs. Our analysis revealed 294 up-regulated DEmRNAs, grouped into the up-cluster, and 407 down-regulated DEmRNAs, forming the down-cluster. Key hub genes in the PPI network, such as Rhof, Vav1, Lyz2, Rab3a, Lyn, Cyfip1, Gns, and Nckap1l, were identified. Additionally, the study successfully constructed a competing endogenous RNA (ceRNA) network, revealing 55 unique lncRNA-miRNA-mRNA link pairs. Our research established a ceRNA network associated with SCI, identifying several critical lncRNA-miRNA-mRNA connection pairs integral to the disease's onset and progression. Notably, significant associations, including the AABR07041411.1-miR-125a-5p-Slc4a7 and the Smg1-rno-miR-331-3p-Tlr4 pairs, were observed to exert a significant influence within this biological context., Competing Interests: Declarations. Ethics Approval and Consent to Participate: All animal experiments were carried out in accordance with the guidelines and regulations approved by the Ethics Committee of The Second Hospital of Jilin University. All methods were carried out in accordance with relevant guidelines and regulations. All methods are reported in accordance with ARRIVE guidelines. Consent for Publication: Not applicable. Conflict of Interest: The author declares no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pancreatic cancer (PaC) incidence is increasing, but our current screening and diagnostic strategies are not very effective. However, screening could be helpful in the case of PaC, as recent evidence shows that the disease progresses gradually. Unfortunately, there is no ideal screening method or program for detecting PaC in its early stages. Conventional imaging techniques, such as abdominal ultrasound, CT, MRI, and EUS, have not been successful in detecting early-stage PaC. On the other hand, biomarkers may be a more effective screening tool for PaC and have greater potential for further evaluation compared to imaging. Recent studies on biomarkers and artificial intelligence (AI)-enhanced imaging have shown promising results in the early diagnosis of PaC. In addition to proteins, non-coding RNAs are also being studied as potential biomarkers for PaC. This review consolidates the current literature on PaC screening modalities to provide an organized framework for future studies. While conventional imaging techniques have not been effective in detecting early-stage PaC, biomarkers and AI-enhanced imaging are promising avenues of research. Further studies on the use of biomarkers, particularly non-coding RNAs, in combination with imaging modalities may improve the accuracy of PaC screening and lead to earlier detection of this deadly disease., Competing Interests: Compliance with Ethical Standards Conflict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To rationalise the binding of specific ligands to RNA-quadruplex we investigated several naphthalene diimide ligands that interact with the non-coding region of Pseudorabies virus (PRV). Herein we report on the x-ray structure of the naphthalene diimide ND11 with an RNA G-quadruplex putative forming sequence from rPRV. Consistent with previously observed rPRV sequence it assembles into a bimolecular RNA G-quadruplex consisting of a pair of two tetrads stacked 3' to 5'. We observe that ND11 interacts by binding on both the externally available 5' and 3' quartets. The CUC (loop 1) is structurally altered to enhance the 5' mode of interaction. These loop residues are shifted significantly to generate a new ligand binding pocket whereas the terminal A14 residue is lifted away from the RNA G-quadruplex tetrad plane to be restacked above the bound ND11 ligand NDI core. CD analysis of this family of NDI ligands shows consistency in the spectra between the different ligands in the presence of the rPRV RNA G-quadruplex motif, reflecting a common folded topology and mode of ligand interaction. FRET melt assay confirms the strong stabilising properties of the tetrasubstituted NDI compounds and the contributions length of the substituted groups have on melt temperatures., Competing Interests: Declaration of competing interest We have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In the snoRNA host gene SNHG14, 29 consecutive introns each generate SNORD116, and 48 tandem introns encode SNORD115. Loss of SNORD116 expression, but not of SNORD115, is linked to the neurodevelopmental disease Prader-Willi syndrome. SNORD116 and SNORD115 resemble box C/D small nucleolar RNAs (snoRNAs) but lack known targets. Both were strongly accumulated during neuronal differentiation, but with distinct mechanisms: Increased host-gene expression for SNORD115 and apparent stabilization for SNORD116. For functional characterization we created cell lines specifically lacking the expressed, paternally inherited, SNORD115 or SNORD116 cluster. Analyses during neuronal development indicates changes in RNA stability and protein synthesis. These data suggest that the loss of SNORD116 enhances some aspects of developmental timing of neuronal cells. Altered mRNAs include MAGEL2, causal in the PWS-like disorder Schaaf-Yang syndrome. Comparison of SNORD115 and SNORD116 mutants identifies small numbers of altered mRNAs and ncRNAs. These are enriched for functions potentially linked to PWS phenotypes and include protocadherins, which are key cell signalling factors during neurodevelopment., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

It was previously thought that ncRNA could not encode polypeptides, but recent reports have challenged this notion. As research into ncRNA progresses, it is increasingly clear that it serves roles beyond traditional mechanisms, playing significant regulatory roles in various diseases, notably cancer, which is responsible for 70% of human deaths. Numerous studies have highlighted the diverse regulatory mechanisms of ncRNA that are pivotal in cancer initiation and progression. The role of ncRNA-encoded polypeptides in cancer regulation has gained prominence. This article explores the newly identified regulatory functions of these polypeptides in three types of ncRNA-lncRNA, pri-miRNA, and circRNA. These polypeptides can interact with proteins, influence signaling pathways, enhance miRNA stability, and regulate cancer progression, malignancy, resistance, and other clinical challenges. Furthermore, we discuss the evolutionary significance of these polypeptides in the transition from RNA to protein, examining their emergence and conservation throughout evolution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Lampbrush chromosomes, with their unusually high rate of nascent RNA synthesis, provide a valuable model for studying mechanisms of global transcriptome up-regulation. Here, we obtained a whole-genomic profile of transcription along the entire length of all lampbrush chromosomes in the chicken karyotype. With nuclear RNA-seq, we obtained information about a wider set of transcripts, including long non-coding RNAs retained in the nucleus and stable intronic sequence RNAs. For a number of protein-coding genes, we visualized their nascent transcripts on the lateral loops of lampbrush chromosomes by RNA-FISH. The set of genes transcribed on the lampbrush chromosomes is required for basic cellular processes and is characterized by a broad expression pattern. We also present the first high-throughput transcriptome characterization of miRNAs and piRNAs in chicken oocytes at the lampbrush chromosome stage. Major targets of predicted piRNAs include CR1 and long terminal repeat (LTR) containing retrotransposable elements. Transcription of tandem repeat arrays was demonstrated by alignment against the whole telomere-to-telomere chromosome assemblies. We show that transcription of telomere-derived RNAs is initiated at adjacent LTR elements. We conclude that hypertranscription on the lateral loops of giant lampbrush chromosomes is required for synthesizing large amounts of transferred to the embryo maternal RNA for thousands of genes., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Noncoding RNA refers to RNA that does not encode proteins. The lncRNA and miRNA it contains play crucial regulatory roles in organisms, and their aberrant expression is closely related to various diseases. Traditional experimental methods for validating the interactions of these RNAs have limitations, and existing prediction models exhibit relatively limited functionality, relying on isolated feature extraction and performing poorly in handling various types of small sample tasks. This paper proposes an improved de Bruijn graph that can inject RNA structural information into the graph while preserving sequence information. Furthermore, the improved de Bruijn graph enables graph neural networks to learn broader dependencies and correlations among data by introducing richer edge relationships. Meanwhile, the multitask learning model, DVMnet, proposed in this paper can handle multiple related tasks, and we optimize model parameters by integrating the total loss of three tasks. This enables multitask prediction of RNA interactions, disease associations, and subcellular localization. Compared with the best existing models in this field, DVMnet has achieved the best performance with a 3% improvement in the area under the curve value and demonstrates robust results in predicting diseases and subcellular localization. The improved de Bruijn graph is also applicable to various scenarios and can unify the sequence and structural information of various nucleic acids into a single graph., (© The Author(s) 2024. Published by Oxford University Press.)

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a critical pathway in cancer biology. This review delves into the epigenetic mechanisms that modulate ferroptosis in cancer cells, focusing on how DNA methylation, histone modifications, and non-coding RNAs influence the expression and function of essential genes involved in this process. By unraveling the complex interplay between these epigenetic mechanisms and ferroptosis, the article sheds light on novel gene targets and functional insights that could pave the way for innovative cancer treatments to enhance therapeutic efficacy and overcome resistance in cancer therapy.

Ribosomal DNA (rDNA) repeats harbor ribosomal RNA (rRNA) genes and intergenic spacers (IGS). RNA polymerase (Pol) I transcribes rRNA genes yielding rRNA components of ribosomes. IGS-associated Pol II prevents Pol I from excessively synthesizing IGS non-coding RNAs (ncRNAs) that can disrupt nucleoli and rRNA production. Here, compartment-enriched proximity-dependent biotin identification (compBioID) revealed the TATA-less-promoter-binding TBPL1 and transcription-regulatory PAF1 with nucleolar Pol II. TBPL1 localizes to TCT motifs, driving Pol II and Pol I and maintaining its baseline ncRNA levels. PAF1 promotes Pol II elongation, preventing unscheduled R-loops that hyper-restrain IGS Pol I-associated ncRNAs. PAF1 or TBPL1 deficiency disrupts nucleolar organization and rRNA biogenesis. In PAF1-deficient cells, repressing unscheduled IGS R-loops rescues nucleolar organization and rRNA production. Depleting IGS Pol I-dependent ncRNAs is sufficient to compromise nucleoli. We present the nucleolar interactome of Pol II and show that its regulation by TBPL1 and PAF1 ensures IGS Pol I ncRNAs maintaining nucleolar structure and function., (© 2024. The Author(s).)

Non-coding RNAs (ncRNAs) have become important modulators of gene expression and biological processes, contributing significantly to the initiation and spread of cancer. This study focuses on the complex interactions between ncRNAs and two major signaling pathways-Wnt/β-catenin signaling and cyclin-dependent kinase (CDK)-linked to cancer. We provide an overview of current research on the modulation of these pathways in many cancer types by distinct classes of ncRNAs, such as miRNAs, lncRNAs, and circRNAs. The review focuses on the processes by which ncRNAs regulate cancer cell survival, proliferation, and metastasis. These mechanical processes include CDK activity, the activation of the Wnt/β-catenin cascade and cell cycle advancement. We also discuss the importance of ncRNAs in drug resistance and treatment outcomes, as well as prognosis markers (diagnostic) and therapeutic targets for cancer. Understanding these complex regulatory networks may help in a large way to improve cancer research and diagnosis - but also perhaps treat patients more effectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Parkinson's Disease is a highly complicated neurological disorder, with a key manifestation of loss of dopaminergic neurons. Despite the plethora of medicines that alleviate the symptoms, there is an urgent need for new treatments acting on the fundamental pathology of PD. Non-coding RNAs are becoming increasingly important in gene regulation and various cellular processes and are found to play a role in PD pathophysiology. This review analyzes the cross-talk of distinct ncRNAs with dopamine signaling. We attempt to constrain the various ncRNA networks that can activate dopamine production. First, we describe the deregulation of miRNAs that target dopamine receptors and have been implicated in PD. Next, we turn to the functions of lncRNAs in dopaminergic neurons and the connections to susceptibility genes for PD. Finally, we will analyze the novel circRNAs, such as ciRS-7, which may modulate dopamine-linked processes and serve as possible PD biomarkers. In this review, we describe recent progress in dopamine neuron revival to treat PD and the therapeutic potential of ncRNA. This review critically evaluates the available data, and we predict the role of some ncRNAs, such as PTBP1, to become candidate treatment targets in the future. Thus, this review aims to summarize the molecular causes for the deficit in dopamine signaling in PD and point to novel ncRNAs-linked therapeutic directions in neuroscience., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Lung cancer is a deadly disease, causing nearly 20 % of all cancer deaths globally. A key factor in lung cancer's development and resistance to treatment is hypoxia, a condition where tumor cells experience low oxygen levels. In this low-oxygen environment, special molecules called non-coding RNAs (ncRNAs) become critical players. NcRNAs, including lncRNAs, miRNAs, circRNAs, and siRNAs, control how genes function and how cells behave. Some ncRNAs, like HIF1A-AS2 and HOTAIR, are linked to the aggressive spread of lung cancer, making them potential targets for therapy. Others, like certain miRNAs, show promise as early detection tools due to their influence on tumor blood vessel formation and metabolism. This complex interplay between hypoxia and ncRNAs is crucial for understanding lung cancer. For example, circRNAs can control the activity of miRNAs, impacting how tumors respond to low oxygen. Additionally, siRNAs offer a potential strategy to overcome treatment resistance caused by hypoxia. By studying the intricate relationship between hypoxia and ncRNAs, scientists hope to uncover new biomarkers for lung cancer. This knowledge will pave the way for developing more effective and targeted treatments for this devastating disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Lung cancer remains an intractable malignancy worldwide, prompting novel therapeutic modalities. Pyroptosis, a lethal form of programmed cell death featured by inflammation, has been involved in cancer progression and treatment response. Simultaneously, non-coding RNA has been shown to have important roles in coordinating pattern formation and oncogenic pathways, including long non-coding RNA (lncRNAs), microRNA (miRNAs), circular RNA (circRNAs), and small interfering RNA (siRNAs). Recent studies have revealed that ncRNAs can promote or inhibit pyroptosis by interacting with key molecular players such as NLRP3, GSDMD, and various transcription factors. This dual role of ncRNAs offers a unique therapeutic potential to manipulate pyroptosis pathways, providing opportunities for innovative cancer treatments. In this review, we integrate current research findings to propose novel strategies for leveraging ncRNA-mediated pyroptosis as a therapeutic intervention in lung cancer. We explore the potential of ncRNAs as biomarkers for predicting patient response to treatment and as targets for overcoming resistance to conventional therapies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Ever since their introduction a decade ago, stable introns, a type of noncoding (nc)RNAs, are found to be key players in different important cellular processes acting through regulation of gene expression and feedback loops to maintain cellular homeostasis. Despite being commonly regarded as useless byproducts, recent studies in yeast suggested that stable introns are essential for cell survivability under starvation. In Drosophila, we found that a stable intron, sisR-1, has a direct effect in regulating mitochondrial dynamics during short-term fasting and subsequently improved overall oocyte quality. We speculated that the beneficial effects implicated by sisR-1 is through the activation of mitohormesis, an interesting phenomenon in mitochondrial biology. Mitohormesis is suggested to improve health span and lifespan of cells and organisms, but the involvement of ncRNAs is not well-documented. Here, we discuss the potential role of sisR-1 and other ncRNAs in activating mitohormesis and the possible applications in improving cellular and organismal health., (© 2024 Wiley Periodicals LLC.)

Drug resistance has compromised the efficacy of chemotherapy. The dysregulation of drug transporters including P-glycoprotein (P-gp) can mediate drug resistance through drug efflux. In this review, we highlight the role of P-gp in cancer drug resistance and the related molecular pathways, including phosphoinositide 3-kinase (PI3K)-Akt, phosphatase and tensin homolog (PTEN) and nuclear factor-κB (NF-κB), along with non-coding RNAs (ncRNAs). Extracellular vesicles secreted by the cells can transport ncRNAs and other proteins to change P-gp activity in cancer drug resistance. P-gp requires ATP to function, and the induction of mitochondrial dysfunction or inhibition of glutamine metabolism can impair P-gp function, thus increasing chemosensitivity. Phytochemicals, small molecules and nanoparticles have been introduced as P-gp inhibitors to increase drug sensitivity in human cancers., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Neuropathic pain (NPP) is a refractory pain syndrome, caused by damage or disease of the somatosensory nervous system and characterized by spontaneous pain, hyperalgesia, abnormal pain and sensory abnormality. Non-coding RNAs (ncRNAs), including microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA) and Piwi interacting RNA (piRNA), play a notable role in initiation and maintenance of NPP. In this review, we summarize the role of ncRNAs in NPP and their underlaying mechanism. Generally, ncRNAs are interacted with mRNA, protein or DNA to regulate the molecules and signals assciated with neuroinflammation, ion channels, neurotrophic factors and others, and then involved in the occurrence and development of NPP. Therefore, this review not only contributes to deepen our understanding of the pathophysiological mechanism of NPP, but also provides theoretical basis for the development of new therapy strategies for this disorder., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cis-regulatory elements (CREs) are integral to the spatiotemporal and quantitative expression dynamics of target genes, thus directly influencing phenotypic variation and evolution. However, many of these CREs become highly susceptible to transcriptional silencing when in a transgenic state, particularly when organised as tandem repeats. We investigated the mechanism of this phenomenon and found that three of the six selected flower-specific CREs were prone to transcriptional silencing when in a transgenic context. We determined that this silencing was caused by the ectopic expression of non-coding RNAs (ncRNAs), which were processed into 24-nt small interfering RNAs (siRNAs) that drove RNA-directed DNA methylation (RdDM). Detailed analyses revealed that aberrant ncRNA transcription within the AGAMOUS enhancer (AGe) in a transgenic context was significantly enhanced by an adjacent CaMV35S enhancer (35Se). This particular enhancer is known to mis-activate the regulatory activities of various CREs, including the AGe. Furthermore, an insertion of 35Se approximately 3.5 kb upstream of the AGe in its genomic locus also resulted in the ectopic induction of ncRNA/siRNA production and de novo methylation specifically in the AGe, but not other regions, as well as the production of mutant flowers. This confirmed that interactions between the 35Se and AGe can induce RdDM activity in both genomic and transgenic states. These findings highlight a novel epigenetic role for CRE-CRE interactions in plants, shedding light on the underlying forces driving hypermethylation in transgenes, duplicate genes/enhancers, and repetitive transposons, in which interactions between CREs are inevitable., (© 2024 The Author(s). Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

The morbidity and mortality rates of cardiovascular diseases (CVDs) are increasing; thus, they impose substantial health and economic burdens worldwide, and effective interventions are needed for immediate resolution of this issue. Recent studies have suggested that noncoding RNAs (ncRNAs) play critical roles in the occurrence and development of CVDs and are potential therapeutic targets and novel biomarkers for these diseases. Newly discovered modes of cell death, including necroptosis, pyroptosis, apoptosis, autophagy-dependent cell death and ferroptosis, also play key roles in CVD progression. However, ferroptosis, which differs from the other aforementioned forms of regulated cell death in terms of cell morphology, biochemistry and inhereditability, is a unique iron-dependent mode of nonapoptotic cell death induced by abnormal iron metabolism and excessive accumulation of iron-dependent lipid peroxides and reactive oxygen species (ROS). Increasing evidence has confirmed that ncRNA-mediated ferroptosis is involved in regulating tissue homeostasis and CVD-related pathophysiological conditions, such as cardiac ischemia/reperfusion (I/R) injury, myocardial infarction (MI), atrial fibrillation (AF), cardiomyopathy and heart failure (HF). In this review, we summarize the underlying mechanism of ferroptosis, discuss the pathophysiological effects of ncRNA-mediated ferroptosis in CVDs and provide ideas for effective therapeutic strategies., (© 2023. The Author(s).)

Aluminum (Al) is known to induce neurotoxic effects, potentially contributing to Alzheimer's disease (AD) pathogenesis. Recent studies suggest that epigenetic modification may contribute to Al neurotoxicity, although the mechanisms are still debatable. Therefore, the objective of the present study was to summarize existing data on the involvement of epigenetic mechanisms in Al-induced neurotoxicity, especially AD-type pathology. Existing data demonstrate that Al exposure induces disruption in DNA methylation, histone modifications, and non-coding RNA expression in brains. Alterations in DNA methylation following Al exposure were shown to be mediated by changes in expression and activity of DNA methyltransferases (DNMTs) and ten-eleven translocation proteins (TETs). Al exposure was shown to reduce histone acetylation by up-regulating expression of histone deacetylases (HDACs) and impair histone methylation, ultimately contributing to down-regulation of brain-derived neurotrophic factor (BDNF) expression and activation of nuclear factor κB (NF-κB) signaling. Neurotoxic effects of Al exposure were also associated with aberrant expression of non-coding RNAs, especially microRNAs (miR). Al-induced patterns of miR expression were involved in development of AD-type pathology by increasing amyloid β (Aβ) production through up-regulation of Aβ precursor protein (APP) and β secretase (BACE1) expression (down-regulation of miR-29a/b, miR-101, miR-124, and Let-7c expression), increasing in neuroinflammation through NF-κB signaling (up-regulation of miR-9, miR-125b, miR-128, and 146a), as well as modulating other signaling pathways. Furthermore, reduced global DNA methylation, altered histone modification, and aberrant miRNA expression were associated with cognitive decline in Al-exposed subjects. However, further studies are required to evaluate the contribution of epigenetic mechanisms to Al-induced neurotoxicity and/or AD development., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Non-coding RNAs (ncRNAs) have key roles in the etiology of many illnesses, including heart failure, myocardial infarction, stroke, and in physiological processes like angiogenesis. In transcriptional regulatory circuits that control heart growth, signaling, and stress response, as well as remodeling in cardiac disease, ncRNAs have become important players. Studies on ncRNAs and cardiovascular disease have made great progress recently. Here, we go through the functions of non-coding RNAs (ncRNAs) like circular RNAs (circRNAs), and microRNAs (miRNAs) as well as long non-coding RNAs (lncRNAs) in modulating cardiovascular disorders., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: RNA binding proteins (RBPs) play a role in sorting non-coding RNAs (ncRNAs) into exosomes. These ncRNAs, carried by exosomes, are involved in regulating various aspects of tumor progression, including metastasis, angiogenesis, control of the tumor microenvironment, and drug resistance. Recent studies have emphasized the importance of the RBP-ncRNA-exosome mechanism in tumor regulation., Aim of Review: This comprehensive review aims to explore the RBP-ncRNA-exosome mechanism and its influence on tumor development. By understanding this intricate mechanism provides novel insights into tumor regulation and may lead to innovative treatment strategies in the future., Key Scientific Concepts of Review: The review discusses the formation of exosomes and the complex relationships among RBPs, ncRNAs, and exosomes. The RBP-ncRNA-exosome mechanism is shown to affect various aspects of tumor biology, including metastasis, multidrug resistance, angiogenesis, the immunosuppressive microenvironment, and tumor progression. Tumor development relies on the transmission of information between cells, with RBPs selectively mediating sorting of ncRNAs into exosomes through various mechanisms, which in turn carry ncRNAs to regulate RBPs. The review also provides an overview of potential therapeutic strategies, such as targeted drug discovery and genetic engineering for modifying therapeutic exosomes, which hold great promise for improving cancer treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Transcriptional silencing by RNAi paradoxically relies on transcription, but how the transition from transcription to silencing is achieved has remained unclear. The Cryptic Loci Regulator complex (CLRC) in Schizosaccharomyces pombe is a cullin-ring E3 ligase required for silencing that is recruited by RNAi. We found that the E2 ubiquitin conjugating enzyme Ubc4 interacts with CLRC and mono-ubiquitinates the histone H3K9 methyltransferase Clr4 SUV39H1 , promoting the transition from co-transcriptional gene silencing (H3K9me2) to transcriptional gene silencing (H3K9me3). Ubiquitination of Clr4 occurs in an intrinsically disordered region (Clr4 IDR ), which undergoes liquid droplet formation in vitro, along with Swi6 HP1 the effector of transcriptional gene silencing. Our data suggests that phase separation is exquisitely sensitive to non-coding RNA (ncRNA) which promotes self-association of Clr4, chromatin association, and di-, but not tri- methylation instead. Ubc4-CLRC also targets the transcriptional co-activator Bdf2 BRD4 , down-regulating centromeric transcription and small RNA (sRNA) production. The deubiquitinase Ubp3 counteracts both activities., (© 2024. The Author(s).)

Treatment of non-small-cell lung cancer (NSCLC) patients possessing EGFR-activating mutations with tyrosine kinase inhibitors (TKIs) can confer an initial promising response. However, TKI resistance inevitably arises. Numerous TKI resistance mechanisms are identified including EGFR secondary mutations, bypass receptor tyrosine kinase (RTK) signaling, and cellular transition e.g. epithelial-mesenchymal transition (EMT). To increase the knowledge of TKI resistance we performed an epigenetic screen to identify small non-coding (nc) genes with DNA methylation alterations in HCC827 NSCLC EGFR-mutated cells with acquired TKI resistance. We analyzed Infinium Methylation EPIC 850K Array data for DNA methylation changes present in both TKI-resistant HCC827 cells with EMT and MET-amplification. Hereby, we identified that the polymorphic maternal imprinted gene nc886 (vtRNA2-1) has a decrease in promoter DNA methylation in TKI-resistant cells. This epigenetic change was associated with an increase in the expression of nc886. The induction of EMT did not affect nc886 expression. CRISPR/Cas9-mediated distortion of the nc886 sequence increased the sensitivity of HCC827 cells towards TKI. Finally, nc886 sequence distortion hindered MET RTK activation and instead was EMT the endpoint TKI resistance mechanism. In conclusion, the expression of nc886 contributes to TKI resistance in the HCC827 NSCLC cell line by supporting cell survival and selection of the endpoint TKI resistance mechanism. We propose DNA methylation and expression changes for nc886 to constitute a novel TKI resistance contributing mechanism in NSCLC., Competing Interests: Declaration of competing interest ‘The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.’, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Although brain amyloid-β (Aβ) peptide buildup is the main cause of Alzheimer's disease (AD), mitochondrial abnormalities can also contribute to the illness's development, as either a primary or secondary factor, as programmed cell death and efficient energy generation depend on the proper operation of mitochondria. As a result, non-coding RNAs (ncRNAs) may play a crucial role in ensuring that nuclear genes related to mitochondria and mitochondrial genes function normally. Interestingly, a significant number of recent studies have focused on the impact of ncRNAs on the expression of nucleus and mitochondrial genes. Additionally, researchers have proposed some intriguing therapeutic approaches to treat and reduce the severity of AD by adjusting the levels of these ncRNAs. The goal of this work was to consolidate the existing knowledge in this field of study by systematically investigating ncRNAs, with a particular emphasis on microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and small nucleolar RNAs (snoRNAs). Therefore, the impact and processes by which ncRNAs govern mitochondrial activity in the onset and progression of AD are thoroughly reviewed in this article. Collectively, the effects of ncRNAs on physiological and molecular mechanisms associated with mitochondrial abnormalities that exacerbate AD are thoroughly reviewed in the current research, while also emphasizing the relationship between disturbed mitophagy in AD and ncRNAs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Type 2 diabetes mellitus (T2DM), a high-incidence chronic metabolic disorder, has emerged as a global health issue, where most patients need lifelong medication. Gaining insights into molecular mechanisms involved in T2DM development is expected to provide novel strategies for clinical prevention and treatment. Growing evidence validates that non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) function as crucial regulators in multiple biological processes of T2DM, inspiring various potential targets and drug candidates. In this review, we summarize the current understanding of ncRNA roles in T2DM and discuss the potential use of ncRNAs as targets and active molecules for drug discovery.

Cancer development is thought to be closely related to aberrant epigenetic regulation, aberrant expression of specific non-coding RNAs (ncRNAs), and tumor microenvironment (TME). The m6A methylation is one of the most abundant RNA modifications found in eukaryotes, and it can determine the fate of RNA at the post-transcriptional level through a variety of mechanisms, which affects important biological processes in the organism. The m6A methylation modification is involved in RNA processing, regulation of RNA nuclear export or localisation, RNA degradation and RNA translation. This process affects the function of mRNAs and ncRNAs, thereby influencing the biological processes of cancer cells. TME accelerates and promotes cancer generation and progression during tumor development. The m6A methylation interacting with ncRNAs is closely linked to TME formation. Mutual regulation and interactions between m6A methylation and ncRNAs in TME create complex networks and mediate the progression of various cancers. In this review, we will focus on the interactions between m6A modifications and ncRNAs in TME, summarising the molecular mechanisms by which m6A interacts with ncRNAs to affect TME and their roles in the development of different cancers. This work will help to deepen our understanding of tumourigenesis and further explore new targets for cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Brassica juncea (L.) Czern is an important oilseed crop affected by various abiotic stresses like drought, heat, and salt. These stresses have detrimental effects on the crop's overall growth, development and yield. Various Transcription factors (TFs) are involved in regulation of plant stress response by modulating expression of stress-responsive genes. The myeloblastosis (MYB) TFs is one of the largest families of TFs associated with various developmental and biological processes such as plant growth, secondary metabolism, stress response etc. However, MYB TFs and their regulation by non-coding RNAs (ncRNAs) in response to stress have not been studied in B. juncea. Thus, we performed a detailed study on the MYB TF family and their interactions with miRNAs and Long non coding RNAs., Results: Computational investigation of genome and proteome data presented a comprehensive picture of the MYB genes and their protein architecture, including intron-exon organisation, conserved motif analysis, R2R3 MYB DNA-binding domains analysis, sub-cellular localization, protein-protein interaction and chromosomal locations. Phylogenetically, BjuMYBs were further classified into different subclades on the basis of topology and classification in Arabidopsis. A total of 751 MYBs were identified in B. juncea corresponding to 297 1R-BjuMYBs, 440 R2R3-BjuMYBs, 12 3R-BjuMYBs, and 2 4R-BjuMYBs types. We validated the transcriptional profiles of nine selected BjuMYBs under drought stress through RT-qPCR. Promoter analysis indicated the presence of drought-responsive cis-regulatory components. Additionally, the miRNA-MYB TF interactions was also studied, and most of the microRNAs (miRNAs) that target BjuMYBs were involved in abiotic stress response and developmental processes. Regulatory network analysis and expression patterns of lncRNA-miRNA-MYB indicated that selected long non-coding RNAs (lncRNAs) acted as strong endogenous target mimics (eTMs) of the miRNAs regulated expression of BjuMYBs under drought stress., Conclusions: The present study has established preliminary groundwork of MYB TFs and their interaction with ncRNAs in B. juncea and it will help in developing drought- tolerant Brassica crops., (© 2024. The Author(s).)

Bone is a connective tissue that is metabolically active and serves multiple functions, including movement, structural support, and organ protection. It is comprised primarily of three types of bone cells, namely osteoblasts, osteocytes, and osteoclasts. Osteoblasts are bone-forming cells, and the differentiation of mesenchymal stem cells towards osteoblasts is regulated by several growth factors, cytokines, and hormones via various signaling pathways, including TGF-β/BMP (transforming growth factor-beta/bone morphogenetic protein) signaling as a primary one. Non-coding RNAs (ncRNAs), such as microRNAs and long ncRNAs, play crucial roles in regulating osteoblast differentiation via the TGF-β/BMP signaling cascade. Dysregulation of these ncRNAs leads to bone-pathological conditions such as osteoporosis, skeletal dysplasia, and osteosclerosis. This review provides a concise overview of the latest advancements in understanding the involvement of ncRNAs/TGF-β/BMP axis in osteoblast differentiation. These findings have the potential to identify new molecular targets for early detection of bone metabolism disorders and the development of innovative therapy strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Epilepsy is a prevalent neurological illness which is linked with high worldwide burdens. Oxidative stress (OS) is recognized to be among the contributors that trigger the advancement of epilepsy, affecting neuronal excitability and synaptic transmission. Various types of non-coding RNAs (ncRNAs) are known to serve vital functions in many disease mechanisms, including epilepsy. The current review sought to understand better the mechanisms through which these ncRNAs regulate epilepsy's OS-related pathways. We investigated the functions of microRNAs in controlling gene expression at the post-translatory stage and their involvement in OS and neuroinflammation. We also looked at the different regulatory roles of long ncRNAs, including molecular scaffolding, enhancer, and transcriptional activator, during OS. Circular RNAs and their capability to act as miRNA decoys and their consequential impact on epilepsy development were also explored. Our review aimed to improve the current understanding of novel therapies for epilepsy based on the role of ncRNAs in OS pathways. We also demonstrated the roles of ncRNAs in epilepsy treatment and diagnosis, explaining that these molecules play vital roles that could be used in therapy as biomarkers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that causes severe outbreaks in human populations. ZIKV infection leads to the accumulation of small non-coding viral RNAs (known as sfRNAs) that are crucial for evasion of antiviral responses and for viral pathogenesis. However, the mechanistic understanding of how sfRNAs function remains incomplete. Here, we use recombinant ZIKVs and ribosome profiling of infected human cells to show that sfRNAs block translation of antiviral genes. Mechanistically, we demonstrate that specific RNA structures present in sfRNAs trigger PKR activation, which instead of limiting viral replication, enhances viral particle production. Although ZIKV infection induces mRNA expression of antiviral genes, translation efficiency of type I interferon and interferon stimulated genes were significantly downregulated by PKR activation. Our results reveal a novel viral adaptation mechanism mediated by sfRNAs, where ZIKV increases its fitness by repurposing the antiviral role of PKR into a proviral factor., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Breast cancer is a significant global health issue. Tumor-associated macrophages (TAMs) are crucial in influencing the tumor microenvironment and the progression of the disease. TAMs exhibit remarkable plasticity in adopting distinct phenotypes ranging from pro-inflammatory and anti-tumorigenic (M1-like) to immunosuppressive and tumor-promoting (M2-like). This review elucidates the multifaceted roles of TAMs in driving breast tumor growth, angiogenesis, invasion, and metastatic dissemination. Significantly, it highlights the intricate crosstalk between TAMs and non-coding RNAs (ncRNAs), including microRNAs, long noncoding RNAs, and circular RNAs, as a crucial regulatory mechanism modulating TAM polarization and functional dynamics that present potential therapeutic targets. Nanotechnology-based strategies are explored as a promising approach to reprogramming TAMs toward an anti-tumor phenotype. Various nanoparticle delivery systems have shown potential for modulating TAM polarization and inhibiting tumor-promoting effects. Notably, nanoparticles can deliver ncRNA therapeutics to TAMs, offering unique opportunities to modulate their polarization and activity.

This review concerns nc886, a 101-nucleotide non-coding RNA (ncRNA). Because nc886 is transcribed by RNA polymerase III (Pol III) and contains a CpG island in its promoter region, its expression is regulated by several transcription factors and the DNA methylation status. These features drive nc886 expression in two opposing directions during tumorigenesis. The known function of nc886 is to bind to and modulate the activity of target proteins such as PKR, Dicer, and OAS1. By being differentially expressed during tumorigenesis and interacting with these proteins, nc886 plays a role in tumor surveillance, promotes or suppresses tumorigenesis, and influences the efficacy of cancer therapy. The multiple roles of nc886 have been well-documented in the literature. In this review, we have summarized this literature and critically discussed the roles and mechanisms of action of nc886 in various cancers.

Reverse transcription has frequently been co-opted for cellular functions and in prokaryotes is associated with protection against viral infection, but the underlying mechanisms of defense are generally unknown. Here, we show that in the DRT2 defense system, the reverse transcriptase binds a neighboring pseudoknotted noncoding RNA. Upon bacteriophage infection, a template region of this RNA is reverse transcribed into an array of tandem repeats that reconstitute a promoter and open reading frame, allowing expression of a toxic repetitive protein and an abortive infection response. Biochemical reconstitution of this activity and cryo-electron microscopy provide a molecular basis for repeat synthesis. Gene synthesis from a noncoding RNA is a previously unknown mode of genetic regulation in prokaryotes.

Defense-associated reverse transcriptase (DRT) systems perform DNA synthesis to protect bacteria against viral infection, but the identities and functions of their DNA products remain largely unknown. We show that DRT2 systems encode an unprecedented immune pathway that involves de novo gene synthesis through rolling circle reverse transcription of a noncoding RNA (ncRNA). Programmed template jumping on the ncRNA generates a concatemeric cDNA, which becomes double-stranded upon viral infection. This DNA product constitutes a protein-coding, nearly endless open reading frame ( neo ) gene whose expression leads to potent cell growth arrest, restricting the viral infection. Our work highlights an elegant expansion of genome coding potential through RNA-templated gene creation and challenges conventional paradigms of genetic information encoded along the one-dimensional axis of genomic DNA.

High-throughput sequencing methods have led to the discovery of many non-coding RNAs, RNA modifications, and protein-RNA interactions. While the list keeps growing, the challenge of determining their functions remains. For our focus issue on RNA biology, we spoke with several researchers about their perspective on investigating the functions of RNA., Competing Interests: Declaration of interests L.Y. has an immediate family member on Molecular Cell’s advisory board. W.V.G. is a founder of Cloverleaf Bio and a member of its scientific advisory board. C.Y. has applied patents for a quantitative m(6)A detection method., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by synovial hyperplasia, and fibroblast-like synoviocytes (FLSs) constitute the majority of cells in the synovial tissue, playing a crucial role in the onset of RA. Dysregulation of FLSs function is a critical strategy in treating joint damage associated with RA. Non-coding RNAs, a class of RNA molecules that do not encode proteins, participate in the development of various diseases. This article aims to review the progress in the study of long non-coding RNAs, microRNAs, and circular RNAs in FLSs. Non-coding RNAs are involved in the pathogenesis of RA, directly or indirectly regulating FLSs' proliferation, migration, invasion, apoptosis, and inflammatory responses. Furthermore, non-coding RNAs also influence DNA methylation and osteogenic differentiation in FLSs. Therefore, non-coding RNAs hold promise as biomarkers for diagnosing RA. Targeting non-coding RNAs in FLSs locally represents a potential strategy for future therapies in RA., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

The gastrointestinal tract is chronically inflamed in ulcerative colitis (UC), which has a complicated etiology involving immunological, environmental, and genetic factors. The inflammatory response that is typical of UC is significantly regulated via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Latest research has displayed that NF-κB signaling is controlled by three main types of non-coding RNAs (ncRNAs): circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs). These ncRNAs can change the expression of key genes within the NF-κB pathway by acting as molecular sponges, transcriptional regulators, and epigenetic modifiers. This review synthesizes current knowledge on the functions by which ncRNAs modulate NF-κB signaling in UC, discusses their potential as biomarkers for disease prognosis and diagnosis, and explores their therapeutic potential. Understanding the intricate interactions between ncRNAs and NF-κB signaling may provide novel insights into UC pathogenesis and targeted therapeutic strategies., Competing Interests: Declaration of Competing Interest The authors declare no competing interests, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Cancer-associated fibroblasts are the most important cellular component of the tumor microenvironment, controlling cancer progression and therapeutic response. These cells in the tumor microenvironment regulate tumor progression and development as oncogenic or tumor suppressor agents. However, the mechanisms by which CAFs communicate with cancer cells remain to investigate. Here, we review evidence that extracellular vesicles, particularly exosomes, serve as vehicles for the intercellular transfer of bioactive cargos, notably microRNAs and long non-coding RNAs, from CAFs to cancer cells. We try to highlight molecular pathways of non-coding RNAs and the interaction among these molecules. Together, these findings elucidate a critical exosome-based communication axis by which CAFs create mostly a supportive pro-tumorigenic microenvironment and highlight therapeutic opportunities for disrupting this intercellular crosstalk., Competing Interests: Declaration of Competing Interest Authors have no financial and non-financial conflict of interest. Both Authors have been agreed in submission of this manuscript to the Pathology - Research and Practice., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Ovarian cancer (OC) is a common gynecological disease with a high mortality rate worldwide due to its insidious nature and undetectability at an early stage. The standard treatment, combining platinum‑based chemotherapy with cytoreductive surgery, has suboptimal results. Therefore, early diagnosis of OC is crucial. All cell types secrete extracellular vesicles, particularly exosomes. Exosomes, which contain lipids, proteins, DNA and non‑coding RNAs (ncRNAs), are novel methods of intercellular communication that participate in tumor development and progression. ncRNAs are categorized by size into long ncRNAs (lncRNAs) and small ncRNAs (sncRNAs). sncRNAs further include transfer RNAs, small nucleolar RNAs, PIWI‑interacting RNAs and microRNAs (miRNAs). miRNAs inhibit protein translation and promote messenger RNA (mRNA) cleavage to suppress gene expression. By sponging downstream miRNAs, lncRNAs and circular RNAs can regulate target gene expression, thereby weakening the interactions between miRNAs and mRNAs. Exosomes and exosomal ncRNAs, commonly present in human biological fluids, are promising biomarkers for OC. The present article aimed to review the potential role of exosomal ncRNAs in the diagnosis and prognosis of OC by summarizing the characteristics, processes, roles and isolation methods of exosomes and exosomal ncRNAs.

Liver fibrosis is a pathological process caused by a variety of chronic liver diseases. Currently, therapeutic options for liver fibrosis are very limited, highlighting the urgent need to explore new treatment approaches. Epigenetic modifications and epitranscriptomic modifications, as reversible regulatory mechanisms, are involved in the development of liver fibrosis. In recent years, researches in epitranscriptomics and epigenetics have opened new perspectives for understanding the pathogenesis of liver fibrosis. Exploring the epigenetic mechanisms of liver fibrosis may provide valuable insights into the development of new therapies for chronic liver diseases. This review primarily focus on the regulatory mechanisms of N6-methyladenosine (m6A) modification, non-coding RNA, and DNA methylation in organ fibrosis. It discusses the interactions between m6A modification and DNA methylation, as well as between m6A modification and non-coding RNA, providing a reference for understanding the interplay between epitranscriptomics and epigenetics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ripening is one of the most important stages of fruit development and determines the fruit quality. Various factors play a role in this process, with epigenetic mechanisms emerging as important players. Epigenetic regulation encompasses DNA methylation, histone modifications and variants, chromatin remodeling, RNA modifications, and non-coding RNAs. Over the past decade, studies using tomato as a model have made considerable progress in understanding the impact of epigenetic regulation on fleshy fruit ripening and quality. In this paper, we provide an overview of recent advancements in the epigenetic regulation of tomato fruit ripening and quality regulation, focusing on three main mechanisms: DNA/RNA modifications, non-coding RNAs, and histone modifications. Furthermore, we highlight the unresolved issues and challenges within this research field, offering perspectives for future investigations to drive agricultural innovation., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

N6-methyladenosine (m 6 A) is one of the most prevalent and reversible forms of RNA methylation, with increasing evidence indicating its critical role in numerous physiological and pathological processes. m 6 A catalyzes messenger RNA(mRNA) as well as regulatory non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs, and circular RNAs. This modification modulates ncRNA fate and cell functions in various bioprocesses, including ncRNA splicing, maturity, export, and stability. Key m 6 A regulators, including writers, erasers, and readers, have been reported to modify the ncRNAs involved in fibrogenesis. NcRNAs affect fibrosis progression by targeting m 6 A regulators. The interactions between m 6 A and ncRNAs can influence multiple cellular life activities. In this review, we discuss the impact of the interaction between m 6 A modifications and ncRNAs on the pathological mechanisms of fibrosis, revealing the possibility of these interactions as diagnostic markers and therapeutic targets in fibrosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Cachexia is a late consequence of various diseases that is characterized by systemic muscle loss, with or without fat loss, leading to significant mortality. Multiple signaling pathways and molecules that increase catabolism, decrease anabolism, and interfere with muscle regeneration are activated. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play vital roles in cachexia muscle atrophy. This review mainly provides the mechanisms of specific ncRNAs to regulate muscle loss during cachexia and discusses the role of ncRNAs in cachectic biomarkers and novel therapeutic strategies that could offer new insights for clinical practice.

All Food and Drug Administration-approved noncoding RNA (ncRNA) drugs (n≈20) target known disease-causing molecular pathways by mechanisms such as antisense. In a fortuitous evolution of work on regenerative medicine, my coworkers and I inverted the RNA drug discovery process: first we identified natural disease-modifying ncRNAs, then used them as templates for new synthetic RNA drugs. Mechanism was probed only after bioactivity had been demonstrated. The journey began with the development of cardiosphere-derived cells (CDCs) for cardiac regeneration. While testing CDCs in a first-in-human trial, we discovered they worked indirectly: ncRNAs within CDC-secreted extracellular vesicles mediate the therapeutic benefits. The vast majority of such ncRNAs are fragments of unknown function. We chose several abundant ncRNA species from CDC-secreted extracellular vesicles, synthesized and screened each of them in vitro and in vivo. Those with exceptional disease-modifying bioactivity inspired new chemical entities that conform to the structural conventions of the Food and Drug Administration-approved ncRNA armamentarium. This discovery arc-Cell-Derived RNA from Extracellular vesicles for bioinspired Drug develOpment, or CREDO-has yielded various promising lead compounds, each of which works via a unique, and often novel, mechanism. The process relies on emergent insights to shape therapeutic development. The initial focus of our inquiry-CDCs-are now themselves in phase 3 testing for Duchenne muscular dystrophy and its associated cardiomyopathy. But the intravenous delivery strategy and the repetitive dosing protocol for CDCs, which have proven key to clinical success, both arose from systematic mechanistic inquiry. Meanwhile, emergent insights have led to multiple cell-free therapeutic candidates: CDC-secreted extracellular vesicles are in preclinical development for ventricular arrhythmias, while the CREDO-conceived RNA drugs are in translation for diseases ranging from myocarditis to scleroderma., Competing Interests: E. Marbán holds founder’s equity in Capricor, Inc.