Search

Background: Milk is essential for mammalian nutrition because it provides vital nutrients for growth and development. Milk composition, which is influenced by genetic and environmental factors, supports lactation, a complex process crucial for milk production and quality. Recent research has focused on noncoding RNAs, particularly microRNAs (miRNAs), which are present in body fluids and regulate gene expression post-transcriptionally. This study comprehensively characterizes miRNAs in milk of four livestock species, namely Bubalus bubalis, Capra hircus, Equus asinus, and Ovis aries and identifies potential target genes., Results: High-throughput sequencing of milk RNA resulted in distinct read counts across species: B. bubalis (8,790,441 reads), C. hircus (12,976,275 reads), E. asinus (9,385,067 reads), and O. aries (7,295,297 reads). E. asinus had the highest RNA mapping rate (94.6%) and O. aries the lowest (84.8%). A substantially greater proportion of miRNAs over other small RNAs was observed for the donkey milk sample (7.74%) compared to buffalo (0.87%), goat (1.57%), and sheep (1.12%). Shared miRNAs, which included miR-200a, miR-200b, miR-200c, and miR-23a among others, showed varying expression levels across species, confirmed by qPCR analysis. Functional annotation of predicted miRNA target genes highlighted diverse roles, with an enrichment in functions linked to metabolism and immunity. Pathway analysis identified immune response pathways as significant, with several miRNAs targeting specific genes across species, suggesting their regulatory function in milk., Conclusions: Both conserved and species-specific miRNAs were detected in milk of the investigated species. The identified target genes of these miRNAs have important roles in neonatal development, adaptation, growth, and immune response. Furthermore, they influence milk and meat production traits in livestock., (© 2024. The Author(s).)

Intramuscular fat (IMF) content significantly impacts meat quality. influenced by complex interactions between skeletal muscle cells and adipocytes. Adipogenesis plays a pivotal role in IMF formation. Exosomes, extracellular membranous nanovesicles, facilitate intercellular communication by transporting proteins, nucleic acids (DNA and RNA), and other biomolecules into target cells, thereby modulating cellular behaviors. Recent studies have linked exosome-derived microRNAs (miRNAs) and other cargo to adipogenic processes. Various cell types, including skeletal muscle cells, interact with adipocytes via exosome secretion and uptake. Exosomes entering adipocytes regulate adipogenesis by modulating key signaling pathways, thereby influencing the extent and distribution of IMF deposition. This review comprehensively explores the origin, formation, and mechanisms of exosome action, along with current research and their applications in adipogenesis. Emphasis is placed on exosome-mediated regulation of miRNAs, non-coding RNAs (ncRNAs), proteins, lipids, and other biomolecules during adipogenesis. Leveraging exosomal contents for genetic breeding and treating obesity-related disorders is discussed. Insights gathered contribute to advancing understanding and potential therapeutic applications of exosome-regulated adipogenesis mechanisms., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Noncoding RNAs (ncRNAs) do not participate in protein-coding. Ferroptosis is a newly discovered form of cell death mediated by reactive oxygen species and lipid peroxidation. Recent studies have shown that ncRNAs such as microRNAs, long noncoding RNAs, circular RNAs, and ferroptosis are involved in the occurrence and development of osteosarcoma (OS). Studies have confirmed that ncRNAs participate in the development of OS by regulating the ferroptosis. However, systematic summary on this topic are still lacking. This review summarises the potential role of ncRNAs in the diagnosis, treatment, drug resistance, and prognosis of OS and the basis for diagnosing, preventing, and treating clinical OS and developing effective drugs. This review summarises the latest research progress on ncRNAs that regulate ferroptosis in OS, attempts to clarify the molecular mechanisms by which ncRNAs regulate ferroptosis in the pathogenesis of OS, and elaborates on the involvement of ferroptosis in OS from the perspective of ncRNAs., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. 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.)

Glioblastoma (GBM) is the most prevalent and deadly primary brain tumor type, with a discouragingly low survival rate and few effective treatments. An important function of the EGFR signalling pathway in the development of GBM is to affect tumor proliferation, persistence, and treatment resistance. Advances in molecular biology in the last several years have shown how important ncRNAs are for controlling a wide range of biological activities, including cancer progression and development. NcRNAs have become important post-transcriptional regulators of gene expression, and they may affect the EGFR pathway by either directly targeting EGFR or by modifying important transcription factors and downstream signalling molecules. The EGFR pathway is aberrantly activated in response to the dysregulation of certain ncRNAs, which has been linked to GBM carcinogenesis, treatment resistance, and unfavourable patient outcomes. We review the literature on miRNAs, circRNAs and lncRNAs that are implicated in the regulation of EGFR signalling in GBM, discussing their mechanisms of action, interactions with the signalling pathway, and implications for GBM therapy. Furthermore, we explore the potential of ncRNA-based strategies to overcome resistance to EGFR-targeted therapies, including the use of ncRNA mimics or inhibitors to modulate the activity of key regulators within the pathway., 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.)

The tissue damage caused by transient ischemic injury is an essential component of the pathogenesis of retinal ischemia, which mainly hinges on the degree and duration of interruption of the blood supply and the subsequent damage caused by tissue reperfusion. Some research indicated that the retinal injury induced by ischemia-reperfusion (I/R) was related to reperfusion time.In this study, we screened the differentially expressed circRNAs, lncRNAs, and mRNAs between the control and model group and at different reperfusion time (24h, 72h, and 7d) with the aid of whole transcriptome sequencing technology, and the trend changes in time-varying mRNA, lncRNA, circRNA were obtained by chronological analysis. Then, candidate circRNAs, lncRNAs, and mRNAs were obtained as the intersection of differentially expression genes and trend change genes. Importance scores of the genes selected the key genes whose expression changed with the increase of reperfusion time. Also, the characteristic differentially expressed genes specific to the reperfusion time were analyzed, key genes specific to reperfusion time were selected to show the change in biological process with the increase of reperfusion time.As a result, 316 candidate mRNAs, 137 candidate lncRNAs, and 31 candidate circRNAs were obtained by the intersection of differentially expressed mRNAs, lncRNAs, and circRNAs with trend mRNAs, trend lncRNAs and trend circRNAs, 5 key genes (Cd74, RT1-Da, RT1-CE5, RT1-Bb, RT1-DOa) were selected by importance scores of the genes. The result of GSEA showed that key genes were found to play vital roles in antigen processing and presentation, regulation of the actin cytoskeleton, and the ribosome. A network included 4 key genes (Cd74, RT1-Da, RT1-Bb, RT1-DOa), 34 miRNAs and 48 lncRNAs, and 81 regulatory relationship axes, and a network included 4 key genes (Cd74, RT1-Da, RT1-Bb, RT1-DOa), 9 miRNAs and 3 circRNAs (circRNA_10572, circRNA_03219, circRNA_11359) and 12 regulatory relationship axes were constructed, the subcellular location, transcription factors, signaling network, targeted drugs and relationship to eye diseases of key genes were predicted. 1370 characteristic differentially expressed mRNAs (spec_24h mRNA), 558 characteristic differentially expressed mRNAs (spec_72h mRNA), and 92 characteristic differentially expressed mRNAs (spec_7d mRNA) were found, and their key genes and regulation networks were analyzed.In summary, we screened the differentially expressed circRNAs, lncRNAs, and mRNAs between the control and model groups and at different reperfusion time (24h, 72h, and 7d). 5 key genes, Cd74, RT1-Da, RT1-CE5, RT1-Bb, RT1-DOa, were selected. Key genes specific to reperfusion time were selected to show the change in biological process with the increased reperfusion time. These results provided theoretical support and a reference basis for the clinical treatment., (© 2024. The Author(s).)

Diabetic cardiomyopathy, a multifaceted complication of diabetes mellitus, remains a major challenge in clinical management due to its intricate pathophysiology. Emerging evidence underscores the pivotal role of autophagy dysregulation in the progression of diabetic cardiomyopathy, providing a novel avenue for therapeutic intervention. Noncoding RNAs (ncRNAs), a diverse class of regulatory molecules, have recently emerged as promising candidates for targeted therapeutic strategies. The exploration of various classes of ncRNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) reveal their intricate regulatory networks in modulating autophagy and influencing the pathophysiological processes associated with diabetic cardiomyopathy. The nuanced understanding of the molecular mechanisms underlying ncRNA-mediated autophagic regulation offers a rationale for the development of precise and effective therapeutic interventions. Harnessing the regulatory potential of ncRNAs presents a promising frontier for the development of targeted and personalized therapeutic strategies, aiming to ameliorate the burden of diabetic cardiomyopathy in affected individuals. As research in this field advances, the identification and validation of specific ncRNA targets hold immense potential for the translation of these findings into clinically viable interventions, ultimately improving outcomes for patients with diabetic cardiomyopathy. This review encapsulates the current understanding of the intricate interplay between autophagy and diabetic cardiomyopathy, with a focus on the potential of ncRNAs as therapeutic targets., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: There is no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Aims: The aim of this review is to systematically summarize and analyze the noncoding RNAs (ncRNAs), especially microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), in the cell apoptosis among Alzheimer's disease (AD) in recent years to demonstrate their value in the diagnosis and treatment of AD., Methods: We systematically summarized in vitro and in vivo studies focusing on the ncRNAs in the regulation of cell apoptosis among AD in PubMed, ScienceDirect, and Google Scholar., Results: We discover three patterns of ncRNAs (including 'miRNA-mRNA', 'lncRNA-miRNA-mRNA', and 'circRNA-miRNA-mRNA') form the ncRNA-based regulatory networks in regulating cell apoptosis in AD., Conclusions: This review provides a future diagnosis and treatment strategy for AD patients based on ncRNAs., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Down syndrome (DS) is the most example of aneuploidy, resulting from an additional copy of all or part of chromosome 21. Competing endogenous RNAs (ceRNAs) play important roles in neuronal development and neurological defects. This study aimed to identify hub genes and synergistic crosstalk among ceRNAs in the DS fetal hippocampus as potential targets for the treatment of DS-related neurodegenerative diseases. We profiled differentially expressed long non-coding RNAs (DElncRNAs), differentially expressed circular RNAs (DEcircRNAs), differentially expressed microRNAs (DEmiRNAs), and differentially expressed messenger RNAs (DEmRNAs) in hippocampal samples from patients with or without DS. Functional enrichment analysis and gene set enrichment analysis were performed, and chromosome 21-related ceRNA and protein-protein interaction networks were constructed. Additionally, the correlations between lncRNA-mRNA and miRNA-mRNA expression in the samples and HEK293T cells were validated. Our finding of changes in the expression of some key genes and ncRNAs on chromosome 21 in DS might not fully conform to the gene dosage hypothesis. Moreover, we found that four lncRNAs (MIR99AHG, PLCB4, SNHG14, GIGYF2) and one circRNA (hsa_circ_0061697) may competitively bind with three miRNAs (hsa-miR-548b-5p, miR-730-5p, and hsa-miR-548i) and subsequently regulate five mRNAs (beta-1,3-galactosyltransferase 5 [B3GALT5], helicase lymphoid-specific [HELLS], thrombospondin-2 [THBS2], glycinamide ribonucleotide transformylase [GART], clathrin heavy chain like 1 [CLTCL1]). These RNAs, whether located on chromosome 21 or not, interact with each other and might activate the PI3K/Akt/mTOR and Wnt signaling pathways, which are involved in autophagosome formation and tau hyperphosphorylation, possibly leading to adverse consequences of trisomy 21. These findings provide researchers with a better understanding of the fundamental molecular mechanisms underlying DS-related progressive defects in neuronal development., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hepatitis is a worldwide health issue that causes inflammation of the liver and is frequently brought on by viral infections, specifically those caused by the hepatitis B and C viruses. Although the pathophysiological causes of hepatitis are complex, recent research indicates that noncoding RNAs (ncRNAs) play a crucial role in regulating apoptosis, an essential process for maintaining liver homeostasis and advancing the illness. Noncoding RNAs have been linked to several biological processes, including apoptosis. These RNAs include microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Distinct expression patterns characterising different stages of the disease have been discovered, indicating dysregulation of these non-coding RNAs in liver tissues infected with hepatitis. The complex interplay that exists between these noncoding RNAs and apoptotic effectors, including caspases and members of the Bcl-2 family, plays a role in the precarious equilibrium that regulates cell survival and death during hepatitis. The purpose of this review is to provide an overview of ncRNA-mediated apoptosis in hepatitis, as well as insights into possible therapeutic targets and diagnostic indicators., 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.)

Globally, atherosclerosis a persistent inflammatory condition of the artery walls continues to be the primary cause of cardiovascular illness and death. The ncRNAs are important regulators of important signalling pathways that affect pyroptosis and the inflammatory environment in atherosclerotic plaques. Comprehending the complex interaction between pyroptosis and non-coding RNAs (ncRNAs) offers fresh perspectives on putative therapeutic targets for ameliorating cardiovascular problems linked to atherosclerosis. The discovery of particular non-coding RNA signatures linked to the advancement of atherosclerosis could lead to the creation of novel biomarkers for risk assessment and customised treatment approaches. A thorough investigation of the regulatory networks regulated by these non-coding RNAs has been made possible by the combination of cutting-edge molecular methods and bioinformatics tools. Studying pyroptosis-related ncRNAs in detail appears to be a promising way to advance our understanding of disease pathophysiology and develop focused therapeutic methods as we work to unravel the complex molecular tapestry of atherosclerosis. This review explores the emerging significance of non-coding RNAs (ncRNAs) in the regulation of pyroptosis and their consequential impact on atherosclerosis pathology., Competing Interests: Declaration of Competing Interest The authors declare no confict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Prostate cancer (PCa) is an important worldwide medical concern, necessitating a greater understanding of the molecular processes driving its development. The Wnt/-catenin signaling cascade is established as a central player in PCa pathogenesis, and recent research emphasizes the critical involvement of non-coding RNAs (ncRNAs) in this scenario. This in-depth study seeks to give a thorough examination of the complex relationship between ncRNAs and the Wnt/β-catenin system in PCa. NcRNAs, such as circular RNAs (circRNAs), long ncRNAs (lncRNAs), and microRNAs (miRNAs), have been recognized as essential regulators that modulate numerous facets of the Wnt/β-catenin network. MiRNAs have been recognized as targeting vital elements of the process, either enhancing or inhibiting signaling, depending on their specific roles and targets. LncRNAs participate in fine-tuning the Wnt/β-catenin network as a result of complicated interplay with both upstream and downstream elements. CircRNAs, despite being a relatively recent addition to the ncRNA family, have been implicated in PCa, influencing the Wnt/β-catenin cascade through diverse mechanisms. This article encompasses recent advances in our comprehension of specific ncRNAs that participate in the Wnt/β-catenin network, their functional roles, and clinical relevance in PCa. We investigate their use as screening and predictive indicators, and targets for treatment. Additionally, we delve into the interplay between Wnt/β-catenin and other signaling networks in PCa and the role of ncRNAs within this complex network. As we unveil the intricate regulatory functions of ncRNAs in the Wnt/β-catenin cascade in PCa, we gain valuable insights into the disease's pathogenesis. The implementation of these discoveries in practical applications holds promise for more precise diagnosis, prognosis, and targeted therapeutic approaches, ultimately enhancing the care of PCa patients. This comprehensive review underscores the evolving landscape of ncRNA research in PCa and the potential for innovative interventions in the battle against this formidable malignancy., 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.)

Colorectal cancer (CRC) poses a substantial global challenge, necessitating a deeper understanding of the molecular underpinnings governing its onset and progression. The transforming growth factor beta (TGF-β) network has been a well-recognized cornerstone in advancing CRC. Nevertheless, a recent study has highlighted the growing importance of non-coding RNAs (ncRNAs) in this context. This comprehensive review aims to present an extensive examination of the interaction between ncRNAs and TGF-signaling. Noncoding RNAs (ncRNAs), encompassing circular RNAs (circRNAs), long-ncRNAs (lncRNAs), and microRNAs (miRNAs), have surfaced as pivotal modulators governing various aspects of TGF-β signaling. MiRNAs have been discovered to target elements within the TGF-β signaling, either enhancing or inhibiting signaling, depending on the context. LncRNAs have been associated with CRC progression, functioning as miRNA sponges or directly influencing TGF-β pathway elements. Even circRNAs, a relatively recent addition to the ncRNA family, have impacted CRC, affecting TGF-β signaling through diverse mechanisms. This review encompasses recent progress in comprehending specific ncRNAs involved in TGF-β signaling, their functional roles, and their clinical relevance in CRC. We investigate the possibility of ncRNAs as targets for detection, prognosis, and therapy. Additionally, we explore the interaction of TGF-β and other pathways in CRC and the role of ncRNAs within this intricate network. As we unveil the intricate regulatory function of ncRNAs in the TGF-β signaling in CRC, we gain valuable insights into the disease's pathogenesis. Incorporating these discoveries into clinical settings holds promise for more precise diagnosis, prognosis, and targeted therapeutic approaches, ultimately enhancing the care of CRC patients. This comprehensive review underscores the ever-evolving landscape of ncRNA research in CRC and the potential for novel interventions in the battle against this formidable 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.)

Diabetic retinopathy (DR) is a devastating complication of diabetes, having extensive and resilient effects on those who suffer from it. As yet, the underlying cell mechanisms of this microvascular disorder are largely unclear. Recently, growing evidence suggests that epigenetic mechanisms can be responsible for gene deregulation leading to the alteration of key processes in the development and progression of DR, in addition to the widely recognized pathological mechanisms. It is noteworthy that seemingly unending epigenetic modifications, caused by a prolonged period of hyperglycemia, may be a prominent factor that leads to metabolic memory, and brings epigenetic entities such as non-coding RNA into the equation. Consequently, further investigation is necessary to truly understand this mechanism. Exosomes are responsible for carrying signals from cells close to the vasculature that are participating in abnormal signal transduction to faraway organs and cells by sailing through the bloodstream. These signs indicate metabolic disorders. With the aid of their encased structure, they can store diverse signaling molecules, which then can be dispersed into the blood, urine, and tears. Herein, we summarized various non-coding RNAs (ncRNAs) that are related to DR pathogenesis. Moreover, we highlighted the role of exosomal ncRNAs in this 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 © 2023. Published by Elsevier B.V.)

Ulcerative colitis (UC) is a persistent inflammatory condition affecting the colon's mucosal lining, leading to chronic bowel inflammation. Despite extensive research, the precise molecular mechanisms underlying UC pathogenesis remain elusive. NcRNAs form a category of functional RNA molecules devoid of protein-coding capacity. They have recently surfaced as pivotal modulators of gene expression and integral participants in various pathological processes, particularly those related to inflammatory disorders. The diverse classes of ncRNAs, encompassing miRNAs, circRNAs, and lncRNAs, have been implicated in UC. It highlights their involvement in key UC-related processes, such as immune cell activation, epithelial barrier integrity, and the production of pro-inflammatory mediators. ncRNAs have been identified as potential biomarkers for UC diagnosis and monitoring disease progression, offering promising avenues for personalized medicine. This approach may pave the way for novel, more specific treatments with reduced side effects, addressing the current limitations of conventional therapies. A comprehensive understanding of the interplay between ncRNAs and UC will advance our knowledge of the disease, potentially leading to more effective and personalized treatments for patients suffering from this debilitating condition. This review explores the pivotal role of ncRNAs in the context of UC, shedding light on their possible targets for diagnosis, prognosis, and therapeutic interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Purpose: SYVN1 is an endoplasmic reticulum (ER)-resident E3 ubiquitin ligase that has an essential function along with SEL1L in rheumatoid arthritis (RA) pathogenesis. This study aimed to investigate the changes in the expression of peripheral blood ncRNAs and SYVN1-SEL1L affected by DMARDs treatment., Methods: Twenty-five newly diagnosed RA patients were randomly assigned to receive conventional DMARDs (csDMARDs) and methylprednisolone for six months. The peripheral blood gene expression of SYVN1 and SEL1L and possible regulatory axes, NEAT1, miR-125a-5p, and miR-19b-3p, were evaluated before and after qRT-PCR. We also compared differences between the patients and healthy controls (HCs), and statistical analyses were performed to determine the correlation between ncRNAs with SYVN1-SEL1L and the clinical parameters of RA., Results: Expression of NEAT1 (P = 0.0001), miR-19b-3p (P = 0.007), miR-125a-5p (P = 0.005), and SYVN1 (P = 0.036) was significantly increased in newly diagnosed patients compared to HCs; also, miR-125a-5p, miR-19b-3p, and SYVN1 were significantly overexpressed after treatment (P = 0.001, P = 0.001, and P = 0.005, respectively). NEAT1 was positively correlated with SYVN1, and miR-125a-5p had a negative correlation with anti-cyclic citrullinated peptides. The ROC curve analysis showed the potential role of selected ncRNAs in RA pathogenesis., Conclusion: The results indicate the ineffectiveness of the csDMARDs in reducing SYVN1 expression. The difference in expression of ncRNAs might be useful markers for monitoring disease activity and determining therapeutic responses in RA patients. Key Points • The expression of NEAT1 is significantly upregulated in RA patients compared to HC subjects. • miR-19b-3p, miR-125a-5p, and SYVN1 are significantly upregulated in RA patients compared to HC subjects. • The expression of miR-19b-3p and miR-125a-5p is significantly increased in RA patients after treatment with DMARDs and methylprednisolone. • NEAT1 is positively correlated with SYVN1., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

The typical function of Drosha is participating in cleaving pri-miRNA, the initial step of miRNA biogenesis, in the nucleus. Since Drosha has a double-stranded RNA-binding domain and two RNase III domains, when it binds and/or cleaves other RNA species other than pri-miRNA, Drosha is able to induce a variety of novel biological effects. Moreover, by interacting with other protein, Drosha is able to modify the function of other protein complexes. Recently, diverse non-classical functions of Drosha have been demonstrated, such as promoting DNA damage repair, transcriptional activation and inhibition, pre-mRNA splicing regulation, mRNA destabilization, and virus-host interaction. In this review, we describe these newly discovered functions of Drosha in order to present a panoramic picture of the novel biological processes that Drosha is involved in., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xuan Jiang reports financial support was provided by The Natural Science Foundation of Guangdong Province (No. 2021A1515011345). Xuan Jiang reports financial support was provided by National Natural Science Foundation of China grants (No. 82271899, No.32200927). Xuan Jiang reports financial support was provided by the Program of Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases (No. ZDSYS20220606100803007)., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The growing information currently available on the central role of non-coding RNAs (ncRNAs) including microRNAs (miRNAS) and long non-coding RNAs (lncRNAs) for chronic and degenerative human diseases makes them attractive therapeutic targets. RNAs carry out different functional roles in human biology and are deeply deregulated in several diseases. So far, different attempts to therapeutically target the 3D RNA structures with small molecules have been reported. In this scenario, the development of computational tools suitable for describing RNA structures and their potential interactions with small molecules is gaining more and more interest. Here, we describe the most suitable strategies to study ncRNAs through computational tools. We focus on methods capable of predicting 2D and 3D ncRNA structures. Furthermore, we describe computational tools to identify, design and optimize small molecule ncRNA binders. This review aims to outline the state of the art and perspectives of computational methods for ncRNAs over the past decade., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Roberta Rocca reports financial support was provided by Italian Association for Cancer Research. Stefano Alcaro reports financial support was provided by PRIN., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Glioblastoma (GBM) is a primary brain tumor arising from glial cells. The tumor is highly aggressive, the reason for which it has become the deadliest brain tumor type with the poorest prognosis. Like other cancers, it compromises molecular alteration on genetic and epigenetic levels. Epigenetics refers to changes in gene expression or cellular phenotype without the occurrence of any genetic mutations or DNA sequence alterations in the driver tumor-related genes. These epigenetic changes are reversible, making them convenient targets in cancer therapy. Therefore, we aim to review critical epigenetic dysregulation processes in glioblastoma. We will highlight the significant affected tumor-related pathways and their outcomes, such as regulation of cell cycle progression, cell growth, apoptosis, angiogenesis, cell invasiveness, immune evasion, or acquirement of drug resistance. Examples of molecular changes induced by epigenetic modifications, such as DNA epigenetic alterations, histone post-translational modifications (PTMs), and non-coding RNA (ncRNA) regulation, are highlighted. As understanding the role of epigenetic regulators and underlying molecular mechanisms in the overall pro-tumorigenic landscape of glioblastoma is essential, this literature study will provide valuable insights for establishing the prognostic or diagnostic value of various non-coding transcripts, including miRNAs.

Ischemic cardiomyopathy is treated mainly with thrombolytic drugs, percutaneous coronary intervention, and coronary artery bypass grafting to recanalize blocked vessels. Myocardial ischemia-reperfusion injury (MIRI) is an unavoidable complication of obstructive revascularization. Compared with those of myocardial ischemic injury, few effective therapeutic options are available for MIRI treatment. The pathophysiological mechanisms of MIRI involve the inflammatory response, the immune response, oxidative stress, apoptosis, intracellular Ca 2+ overload, and cardiomyocyte energy metabolism. These mechanisms exacerbate MIRI. Mesenchymal stem cell-derived exosomes (MSC-EXOs) can alleviate MIRI through these mechanisms and, to some extent, prevent the limitations caused by direct MSC administration. Therefore, using MSC-EXOs instead of MSCs to treat MIRI is a potentially beneficial cell-free treatment strategy. In this review, we describe the mechanism of action of MSC-EXO-derived noncoding RNAs in the treatment of MIRI and discuss the advantages and limitations of this strategy, as well as possible future research directions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Septic acute kidney injury (SAKI) is one of the most common and life-threatening complications of sepsis. Patients with SAKI have increased mortality. However, the underlying pathogenesis is unclear, and the treatment targeting SAKI is unsatisfactory. Thus, identifying optimal biomarkers for SAKI diagnosis and treatment is an urgent requisite. Accumulating evidence indicates that noncoding RNAs (ncRNAs) are involved in the occurrence and progression of SAKI. In the present review, we summarized the studies of ncRNAs in SAKI, including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs). The ncRNAs are divided into protective and damage factors according to their role in SAKI, and their expression patterns, functions, and molecular mechanisms were elaborated. Next, we proposed that ncRNAs have the potential to be diagnostic and prognostic biomarkers for SAKI and as new therapeutic targets. This review aimed to provide a comprehensive overview of ncRNAs in SKAI and explored the clinical value of ncRNAs as ideal biomarkers of SAKI., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Although the mechanisms as well as pathways associated with cancer stem cell (CSC) maintenance, expansion, and tumorigenicity have been extensively studied and the role of tumor cell (TC)-derived exosomes in this process is well understood, there is a paucity of research focusing specifically on the functional mechanisms of CSC-derived exosomes (CSC-Exo)/-exosomal-ncRNAs and their impact on malignancy. This shortcoming needs to be addressed, given that these vesicular and molecular components of CSCs could have a great impact on the cancer initiation, progression, and recurrence through their interaction with other key tumor microenvironment (TME) components, such as MSCs/MSC-Exo and CAFs/CAF-Exo. In particular, understanding CSCs/CSC-Exo and its crosstalk with MSCs/MSC-Exo or CAFs/CAF-Exo that are associated with the proliferation, migration, differentiation, angiogenesis, and metastasis through an enhanced process of self-renewal, chemotherapy as well as radiotherapy resistance may aid cancer treatment. This review contributes to this endeavor by summarizing the characteristic features and functional mechanisms of CSC-Exo/MSC-Exo/CAF-Exo and their mutual impact on cancer progression and therapy resistance., Competing Interests: Declaration of competing interest "The authors declare that there are no conflicts of interest.", (Copyright © 2023 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Background: Over the last few decades, research associated with the coding genome, primarily DNA and transcriptome (mRNA, rRNA, and tRNA), has changed our understanding in several aspects, including physiology, diagnostics, and therapeutics. A large proportion of the human genome that encodes proteins is essential for physiology. However, the human genome represents a significantly large proportion of non-translational, i.e., non-coding (nc) RNAs like microRNAs, siRNAs, piRNAs, lncRNAs, and circRNAs. These ncRNAs do not translate into functional proteins but are associated with several events, such as the regulation of gene expression via several mechanisms. Our understanding of ncRNAs has advanced in the last decade, such as microRNAs and siRNAs, but still, several other ncRNAs remain unexplored. The study comprehended the association of ncRNAs in cerebral ischemia., Methods: In this study searches utilizing multiple databases, PubMed, EMBASE, and Google Scholar were made. The literature survey was done on ncRNA including short and lncRNA associated with the onset, and progression of cerebral ischemia. The literature search was also made for the studies associated with the diagnostic and therapeutic role of ncRNAs for cerebral ischemia., Results and Discussion: Reports suggested that both short and long ncRNAs are critical players of gene expression and are hence associated with the pathophysiology of cerebral ischemia. The reports demonstrate ncRNAs precisely lncRNAs and microRNAs are not only associated with cerebral ischemia progression but also potential diagnostic and therapeutic candidates., In Conclusion: This review is certainly helpful to understand the interplay of ncRNAs in understanding gene expression profile and pathophysiology of cerebral ischemia. These ncRNAs molecules show potential for diagnostic and therapeutic development., (© 2022. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Based on recent research, the non-coding genome is essential for controlling genes and genetic programming during development, as well as for health and cardiovascular diseases (CVDs). The microRNAs (miRNAs), lncRNAs (long ncRNAs), and circRNAs (circular RNAs) with significant regulatory and structural roles make up approximately 99% of the human genome, which does not contain proteins. Non-coding RNAs (ncRNA) have been discovered to be essential novel regulators of cardiovascular risk factors and cellular processes, making them significant prospects for advanced diagnostics and prognosis evaluation. Cases of CVDs are rising due to limitations in the current therapeutic approach; most of the treatment options are based on the coding transcripts that encode proteins. Recently, various investigations have shown the role of nc-RNA in the early diagnosis and treatment of CVDs. Furthermore, the development of novel diagnoses and treatments based on miRNAs, lncRNAs, and circRNAs could be more helpful in the clinical management of patients with CVDs. CVDs are classified into various types of heart diseases, including cardiac hypertrophy (CH), heart failure (HF), rheumatic heart disease (RHD), acute coronary syndrome (ACS), myocardial infarction (MI), atherosclerosis (AS), myocardial fibrosis (MF), arrhythmia (ARR), and pulmonary arterial hypertension (PAH). Here, we discuss the biological and clinical importance of miRNAs, lncRNAs, and circRNAs and their expression profiles and manipulation of non-coding transcripts in CVDs, which will deliver an in-depth knowledge of the role of ncRNAs in CVDs for progressing new clinical diagnosis and treatment.

Most of the human genome is transcribed into non-coding RNAs (ncRNAs), which encompass a heterogeneous family of transcripts including microRNAs (miRNAs), long ncRNAs (lncRNAs), circular RNAs (circRNAs), and others. Although the detailed modes of action of some classes are not fully elucidated, the common notion is that ncRNAs contribute to sculpting gene expression of eukaryotic cells at multiple levels. These range from the regulation of chromatin remodeling and transcriptional activity to post-transcriptional regulation of messenger RNA splicing, stability, and decay. Many of these functions ultimately govern the expression of coding and non-coding genes to affect diverse physiological and pathological mechanisms in vascular biology and beyond. As such, different classes of ncRNAs emerged as crucial regulators of vascular integrity as well as active players in the pathophysiology of atherosclerosis from the early stages of endothelial dysfunction to the clinically relevant complications. However, research in recent years revealed unexpected findings such as small ncRNAs being able to biophysically regulate protein function, the glycosylation of ncRNAs to be exposed on the cell surface, the release of ncRNAs in the extracellular space to act as ligands of receptors, and even the ability of non-coding portion of messenger RNAs to mediate structural functions. This evidence expanded the functional repertoire of ncRNAs far beyond gene regulation and highlighted an additional layer of biological control of cell function. In this Review, we will discuss these emerging aspects of ncRNA biology, highlight the implications for the mechanisms of vascular biology and atherosclerosis, and discuss possible translational implications., 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 © 2023 Elsevier B.V. All rights reserved.)

Non-coding RNAs (ncRNAs) are significant regulators of gene expression in a wide range of biological processes, such as transcription, RNA maturation, or translation. ncRNAs interplay with proteins or other RNAs through not only classical sequence-based mechanisms but also unique higher-order structures such as RNA G-quadruplexes (rG4s). rG4s are predictably formed in guanine-rich sequences and are closely related to various human diseases, such as tumors, neurodegenerative diseases, and infections. This review focuses on the vital role of rG4s in ncRNAs, particularly lncRNAs and miRNAs. We outline the dynamic balance between rG4s and RNA stem-loop/hairpin structures and the interplay between ncRNAs and interactors, thereby modulating gene expression and disease progression. A complete understanding of the biological regulatory role and mechanism of rG4s in ncRNAs affirms the critical importance of folding into the appropriate three-dimensional structure in maintaining or modulating the functions of ncRNAs. It makes them novel therapeutic targets for adjusting potential-G4-containing-ncRNAs-associated diseases., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

With the rapid development of next-generation sequencing technology, several studies have shown that ncRNAs can act as competitive endogenous RNAs (ceRNAs) and are involved in various biological processes, such as proliferation, differentiation, apoptosis, and migration of breast cancer (BC) cells, and plays an important role in BC progression as a molecular target for its diagnosis, treatment, prognosis, and differentiation of subtypes and age groups of BC patients. Based on the description of ceRNA-related biological functions, this study screened and sorted the sequencing analysis and experimental verification conclusions of BC-related ceRNAs and found that the ncRNAs mediated ceRNA networks can promote the development of BC by promoting the expression of genes related to BC proliferation, drug resistance, and apoptosis, inducing the production of epithelial-mesenchymal transition (EMT) to promote metastasis and activating cancer-related signaling pathways., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Non-coding RNAs (ncRNAs) are RNAs that do not encode proteins but play important roles in regulating cellular processes. Multiple studies over the past decade have demonstrated the role of microRNAs (miRNAs) in cancer, in which some miRNAs can act as biomarkers or provide therapy target. Accumulating evidence also points to the importance of long non-coding RNAs (lncRNAs) in regulating miRNA-mRNA networks. An increasing number of ncRNAs have been shown to be involved in the regulation of cellular processes, and dysregulation of ncRNAs often heralds disease. As the population ages, the incidence of neurodegenerative diseases is increasing, placing enormous pressure on global health systems. Given the excellent performance of ncRNAs in early cancer screening and treatment, here we attempted to aggregate and analyze the regulatory functions of ncRNAs in neuronal development and disease. In this review, we summarize current knowledge on ncRNA taxonomy, biogenesis, and function, and discuss current research progress on ncRNAs in relation to neuronal development, differentiation, and neurodegenerative diseases., Competing Interests: The authors declare there are no competing interests., (©2023 Xuan et al.)

ncRNAs, particularly miRNAs, lncRNAs and circRNAs, are a group of RNAs which, although they do not encode proteins (however, recent evidence shows that certain circRNAs are translatable), play a major role in regulating gene expression and, therefore, affect multiple cellular processes, in particular apoptosis. Apoptosis is proven to mediate myocardial infarction physiopathology in addition to ischemic necrosis and, therefore, has recently gained great interest as a target to improve MI outcomes. The current work reviews studies that have assessed ncRNAs with the ability to promote or suppress apoptosis in the process of MI and, therefore, may introduce new therapeutic targets for MI treatment.

Non-coding RNAs (ncRNAs) encompass a family of ubiquitous RNA molecules that lack protein-coding potential and have tissue-specific expression. A significant body of evidence indicates that ncRNA's aberrant expression plays a critical role in disease onset and development. NcRNAs' biochemical characteristics such as disease-associated concentration changes, structural stability, and high abundance in body fluids make them promising prognostic and diagnostic biomarkers. Myocardial infarction (MI) is a leading cause of mortality worldwide. Acute myocardial infarction (AMI), the term in use to describe MI's early phase, is generally diagnosed by physical examination, electrocardiogram (ECG), and the presence of specific biomarkers. In this regard, compared to standard MI biomarkers, such as the cardiac troponin isoforms (cTnT & cTnI) and the Creatinine Kinase (CK), ncRNAs appears to provide better sensitivity and specificity, ensuring a rapid and correct diagnosis, an earlier treatment, and consequently a good prognosis for the patients. This review aims to summarize and discuss the most promising and recent data on the potential clinical use of circulating ncRNAs as MI biomarkers. Specifically, we focused primarily on miRNAs and lncRNAs, highlighting their significant specificity and sensitivity, discussing their limitations, and suggesting possible overcoming approaches., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: The procession of preadipocytes differentiation into mature adipocytes involves multiple cellular and signal transduction pathways. Recently. a seirces of noncoding RNAs (ncRNAs), including circular RNAs (circRNAs) were proved to play important roles in regulating differentiation of adipocytes., Result: In this study, we aimed to identificate the potential circRNAs in the early and late stages of goat intramuscular adipocytes differentiation. Using bioinformatics methods to predict their biological functions and map the circRNA-miRNA interaction network. Over 104 million clean reads in goat intramuscular preadipocytes and adipocytes were mapped, of which16 circRNAs were differentially expressed (DE-circRNAs). Furthermore, we used real-time fluorescent quantitative PCR (qRT-PCR) technology to randomly detect the expression levels of 8 circRNAs among the DE-circRNAs, and our result verifies the accuracy of the RNA-seq data. From the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the DE-circRNAs, two circRNAs, circ_0005870 and circ_0000946, were found in Focal adhesion and PI3K-Akt signaling pathway. Then we draw the circRNA-miRNA interaction network and obtained the miRNAs that possibly interact with circ_0005870 and circ_0000946. Using TargetScan, miRTarBase and miR-TCDS online databases, we further obtained the mRNAs that may interact with the miRNAs, and generated the final circRNA-miRNA-mRNA interaction network. Combined with the following GO (Gene Ontology) and KEGG enrichment analysis, we obtained 5 key mRNAs related to adipocyte differentiation in our interaction network, which are FOXO3(forkhead box O3), PPP2CA (protein phosphatase 2 catalytic subunit alpha), EEIF4E (eukaryotic translation initiation factor 4), CDK6 (cyclin dependent kinase 6) and ACVR1 (activin A receptor type 1)., Conclusions: By using Illumina HiSeq and online databases, we generated the final circRNA-miRNA-mRNA interaction network that have valuable functions in adipocyte differentiation. Our work serves as a valuable genomic resource for in-depth exploration of the molecular mechanism of ncRNAs interaction network regulating adipocyte differentiation., (© 2023. The Author(s).)

Sympathetic nerves play essential roles in the regulation of lung inflammation, and we investigated the effect of sympathetic denervation (SD) on sepsis-induced acute lung injury (ALI) in mice. Mice were randomized to the control, SD, ALI and SD + ALI, groups. SD and ALI were established through intratracheal 6-hydroxydopamine and intraperitoneal lipopolysaccharide, respectively. Models and gene expressions levels were evaluated by HE staining, ELISA, Western blotting and RT-qPCR. RNA extraction, whole transcriptome sequencing and subsequent biostatistical analysis were performed. Sympathetic denervation in the lungs significantly attenuated lung TNF-ɑ and norepinephrine expression, alleviated sepsis-induced acute lung injury and inhibited NF-κB signaling. Compared with the ALI group, the SD + ALI group exhibited 629 DE circRNAs, 269 DE lncRNAs,7 DE miRNAs and 186 DE mRNAs, respectively. Some DE RNAs were validated by RT-qPCR. CircRNA-miRNA-mRNA regulatory networks in the SD + ALI group revealed enrichment of the B-cell receptor signaling pathway, IL-17 signaling pathway, neuroactive ligand-receptor interaction, CAM, primary immunodeficiency, and cytokine-cytokine receptor interaction terms. The lncRNA-miRNA-mRNA network also revealed inflammation-related signaling pathways. Taken together, based on the successfully established models of SD and ALI, we show here that sympathetic nerves may regulate sepsis-induced ALI supposedly by affecting the expression of circRNAs, lncRNAs, miRNAs, and mRNAs in the lungs. These results may allow for further exploration of the roles of pulmonary sympathetic nerves in sepsis-induced ALI., (© 2022. The Author(s).)

Breast cancer, as a highly heterogeneous malignant tumor, is one of the primary causes of death among females worldwide. The etiology of breast cancer involves aberrant epigenetic mechanisms and abnormal expression of certain non-coding RNA (ncRNAs). DNA methylation, N6-methyladenosine(m6A), and histone methylation are widely explored epigenetic regulation types in breast cancer. ncRNAs are a group of unique RNA transcripts, mainly including microRNA (miRNAs), long non-coding RNA (lncRNAs), circular RNA (circRNAs), small interfering RNA (siRNAs), piwi-interacting RNA (piRNAs), etc. Different types of methylation and ncRNAs mutually regulate and interact to form intricate networks to mediate precisely breast cancer genesis. In this review, we elaborate on the crosstalk between major methylation modifications and ncRNAs and discuss the role of their interaction in promoting breast cancer oncogenesis. This review can provide novel insights into establishing a new diagnostic marker system on methylation patterns of ncRNAs and therapeutic perspectives of combining ncRNA oligonucleotides and phytochemical drugs for breast cancer therapy.

Background: Despite improvements in anorectal malformation (ARM) therapy, patients might still experience post-operative problems such as fecal incontinence, constipation, and soiling. In particular, the dysplasia of the lumbosacral spinal cord in ARM patients is a major disorder that affects fecal function post-operation. However, the pathological mechanisms involved are still unclear., Methods: The non-coding RNAs (ncRNAs) in the lumbosacral spinal cord of fetal rats with ethylenethiourea-induced ARM were identified using RNA sequencing (RNA-seq) and examined to determine their potential function. The lumbosacral spinal cord was isolated on embryonic day 17 for subsequent RNA extraction and RNA-seq. The transcriptome data was analyzed using bioinformatics analysis, followed by validation using quantitative reverse transcription PCR., Results: Compared to the control group, 26 differentially expressed microRNAs (DEMs; 22 upregulated, 4 downregulated) and 112 differentially expressed long non-coding RNAs (63 upregulated, 49 downregulated) were identified in the ARM group. Several DEMs related to development, namely miR-200a-3p, miR-200b-3p, miR-200c-3p, miR-200a-5p, and miR-429, were selected for further analysis. Notably, compared to the control, the relative expression of miR-200 family members was highly upregulated in ARM fetal rats. Furthermore, GO and KEGG enrichment and miRNA-transcription factor-lncRNA/mRNA network analysis was explored to show molecular mechanism underlying DEMs., Conclusions: Our findings suggest the involvement of ncRNAs, especially the miR-200 family members, in the pathogenesis of lumbosacral spinal cord dysplasia in ARM fetal rats., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver pathology worldwide. Meanwhile, liver cancer represents the sixth most common malignancy, with hepatocellular carcinoma (HCC) as the primary, most prevalent subtype. Due to the rising incidence of metabolic disorders, NAFLD has become one of the main contributing factors to HCC development. However, although NAFLD might account for about a fourth of HCC cases, there is currently a significant gap in HCC surveillance protocols regarding noncirrhotic NAFLD patients, so the majority of NAFLD-related HCC cases were diagnosed in late stages when survival chances are minimal. However, in the past decade, the focus in cancer genomics has shifted towards the noncoding part of the genome, especially on the microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), which have proved to be involved in the regulation of several malignant processes. This review aims to summarize the current knowledge regarding some of the main dysregulated, noncoding RNAs (ncRNAs) and their implications for NAFLD and HCC development. A central focus of the review is on miRNA and lncRNAs that can influence the progression of NAFLD towards HCC and how they can be used as potential screening tools and future therapeutic targets.

RNA molecules lacking capacity in protein translation, are known as non-coding RNAs (ncRNAs). Growth, differentiation and migration are influenced by ncRNAs in cells. The abnormal expression of ncRNAs contributes to development of diseases, especially cancer. On the other hand, EMT is a vital mechanism for cancer invasion and diffusion in body. In this manuscript, role of ncRNAs in EMT regulation and subsequent effect on cancer progression is investigated. The miRNAs regulate EMT by affecting signaling pathways including PI3K/Akt and PTEN to modulate cancer metastasis. Furthermore, miRNA and EMT interaction has close association with drug sensitivity of tumor cells. LncRNAs can affect EMT via targeting ZEB1/2, Twist and Snail among others and similarly, based on the impact on EMT, sensitivity of cancer cells to therapy increases or decreases. CircRNAs regulate both drug sensitivity and metastasis of cancers by affecting EMT mechanism. Noteworthy, circRNAs and lncRNAs are capable of sponging miRNAs in modulating EMT mechanism. Exosomes belong to extracellular vesicles with low size that can be secreted by cells in transferring genetic materials. The transfer of ncRNAs by exosomes is performed and they can also regulate EMT in cancer progression. Finally, ncRNAs regulating EMT mechanism are used for cancer diagnosis and prognosis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Esophageal squamous cell carcinoma (ESCC) is a highly prevalent tumor that requires extensive research. Ferroptosis is a unique cell death modality driven by iron-dependent phospholipid peroxidation manifested as an accumulation of lipid-reactive oxygen species. With further understanding of noncoding RNAs (ncRNAs), numerous studies have demonstrated an important regulatory role of ncRNAs in ESCC through ferroptosis, including microRNAs, long ncRNAs, and circular RNAs. These ncRNAs influence the expression of the target gene to regulate ESCC progression by involving the ferroptosis signaling pathway. However, the specific regulatory mechanism of ncRNAs on ferroptosis in ESCC remains largely unknown. This review summarized the current knowledge on the relation between ferroptosis regulators, such as glutathione synthesis/metabolism, Keap1/Nfr2, and p53, by ncRNAs and ESCC. This review also proposed the possible therapeutic approaches for ncRNAs targeting ferroptosis in ESCC. This is the latest and most effective summary of recent research achievements of ncRNAs on ferroptosis in ESCC. These ncRNAs based on ferroptosis merit further investigation in preclinical research of ESCC., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Platelet activation is commonly detected after infection by multiple viruses such as human immunodeficiency virus (HIV), H1N1 influenza, Hepatitis C virus (HCV), Ebola virus (EBV), and Dengue virus (DENV). Non-coding RNAs (ncRNAs) constitute the majority of the human transcribed genome, but the biology of platelet ncRNAs is largely unexplored. In this study, we performed microarray profiling to characterize the expression profile of human platelets infected with EBV in vitro after 2 h. A total of 187 long non-coding RNAs (lncRNAs) displayed differences, of which 114 were upregulated and 73 were downregulated; 78 microRNAs (miRNAs) showed differences, including 73 upregulated and 5 downregulated; 808 mRNAs displayed differences, among which 367 were upregulated and 441 were downregulated. Gene ontology (GO) analysis mostly related to G protein-coupled receptor signaling pathway, detection of chemical stimulus involved in sensory perception of smell and regulation of transcription by RNA polymerase II. Pathway analysis showed that the differentially expressed genes were mainly enriched in cell metabolism and immune-related response. A ceRNA network was established based on predicting regulatory pairs in differentially expressed genes, in which hsa-miR-6877-3p had the highest regulatory capability (degree = 31), FAM230A was the lncRNA with the highest regulatory capability (degree = 28). According to the EBV related miRNA regulation network, it revealed that ebv-miR-BART19-3p had the most target genes and BRWD1, FAM126B, TFRC and JMY were the genes most regulated by EBV-related miRNAs. After overlapping the three networks, we found that the EIFAK2 gene was strongly correlated with autologous ncRNAs, including hsa-miR-1972, hsa-miR-504-3p and hsa-miR-6825-5p, as well as with EBV ncRNAs, including EBER1, EBER2, miR-BART7-3p and miR-BART16. The present study contributes to a better understanding of the expression profiling of ncRNAs and their functions in platelets activated by EBV in vitro, and paves the way to further study on platelet function., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Heart failure is among the most progressive diseases and a leading cause of morbidity. Despite several advances in cardiovascular therapies, pharmacological treatments are limited to relieve symptoms without curing cardiac injury. Multiple observations point to the involvement of immune cells as key drivers in the pathophysiology of heart failure. In particular, there is a growing recognition that heart failure is related to a prolonged and insufficiently repressed inflammatory response leading to molecular, cellular, and functional cardiac alterations. Over the last decades, non-coding RNAs are recognized as prominent mediators of cardiac inflammation, affecting the function of several immune cells. In the current review, we explore the contribution of the diverse immune cells in the progression of heart failure, revealing mechanistic functions for non-coding RNAs in cardiac immune cells as a new and exciting field of investigation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Approximately 90% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC). PDAC is the fourth leading cause of cancer death world-wide. Therapies for PDAC are largely ineffective due to the dense desmoplastic tumor microenvironment which prevents chemotherapeutic drugs and small molecule inhibitors from exerting effective anti-cancer effects. In this review, we will discuss the roles of TP53 and miRs on the PDAC tumor microenvironment and how loss of the normal functions of TP53 promote tumor progression. The TP53 gene is mutated in approximately 50% of pancreatic cancers. Often, these TP53 mutations are point mutations which confer additional functions for the TP53 proteins. These are called gain of function (GOF) mutations (mut). Another class of TP53 mutations are deletions which result in loss of the TP53 protein; these are referred to TP53-null mutations. We have organized this review into various components/properties of the PDAC microenvironment and how they may be altered in the presence of mutant TP53 and loss of certain miR expression.

The growing knowledge on several classes of non-coding RNAs (ncRNAs) and their different functional roles has aroused great interest in the scientific community. Beyond the Central Dogma of Biology, it is clearly known that not all RNAs code for protein products, and they exert a broader repertoire of biological functions. As described in this review, ncRNAs participate in gene expression regulation both at transcriptional and post-transcriptional levels and represent critical elements driving and controlling pathophysiological processes in multicellular organisms. For this reason, in recent years, a great boost was given to ncRNA-based strategies with potential therapeutic abilities, and nowadays, the use of RNA molecules is experimentally validated and actually exploited in clinics to counteract several diseases. In this review, we summarize the principal classes of therapeutic ncRNA molecules that are potentially implied in disease onset and progression, which are already used in clinics or under clinical trials, highlighting the advantages and the need for a targeted therapeutic strategy design. Furthermore, we discuss the benefits and the limits of RNA therapeutics and the ongoing development of delivery strategies to limit the off-target effects and to increase the translational application.

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by joint damage and even extra-articular involvement. In this study, the gene expression levels of MALAT1, H19 and their possible downstream microRNAs, miR-199a-5p, miR-1-3p, and the predicted targets of these miRNAs, HSPA5 and MMD, were examined., Methods: Twenty-five newly diagnosed RA patients and 25 healthy individuals were included. For six months, patients were treated with conventional disease-modifying antirheumatic drugs (DMARDs) and Methylprednisolone (mPRED). Blood samples were obtained from healthy controls and patients (before and after treatment). After RNA extraction, the RT-qPCR technique was used to evaluate the expression level of the studied genes., Results: Data showed that the expression level of MALAT1, H19, miR-199a-5p, and miR-1-3p was significantly higher in the newly diagnosed patients with RA than the healthy subjects, but the increase in the expression level of HSPA5 and MMD genes in the new cases was not significant compared to healthy controls. After treatment, except for the expression level of lncRNAs, the expression level of miRNAs, HSPA5, and MMD significantly increased. Based on ROC curve analysis of MALAT1, H19, miR-199a-5p and miR-1-3p have a high ability to identify patients from healthy individuals (AUC = 0.986, AUC = 0.995, AUC = 0.855, AUC = 0.675, respectively)., Conclusion: MALAT1 and H19 may be candidates as potential biomarkers for the discrimination between RA patients and controls. DMARDs plus mPRED therapy do not have a desirable effect on reducing inflammatory responses and ER stress., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Whey protein has been reported to be an impactful dietary supplement to ameliorate skeletal muscle aging for a long time. However, whether whey protein could contribute to muscle aging amelioration by post-transcriptional modulation remains unclear. In this study, 19-month-old mice orally received whey protein supplementation (1.0 g/kg/bw/d, whey protein group) or deionized water (the control group) for 3 months. Differentially expressed ncRNAs and mRNAs in quadriceps were identified by RNA-seq. Construction of non-coding RNAs (ncRNAs)-associated competing endogenous RNA (ceRNA) networks as well as GO and KEGG enrichment analyses were also carried out subsequently. Meanwhile, ultrasound measurement, H&E staining, myofiber cross-sectional area measurement, western blotting and RT-qPCR were performed in the quadriceps to evaluate muscle status and verify the RNA-seq data. Whey protein supplementation for 3 months increased quadriceps-body weight ratio and improved the histological as well as ultrasonographic characteristics of aging in muscle. Moreover, the protein expression levels of Myog, Myf4, Myf5 and MyoD1 were all significantly elevated in quadriceps. The expression of 90 lncRNAs, 334 mRNAs, six circRNAs and 52 miRNAs were significantly up or down-regulated in quadriceps after whey protein supplementation. Furthermore, ncRNAs-associated networks and GO and KEGG enrichment analyses revealed whey protein may influence muscle aging process through selected ncRNAs-associated ceRNA networks. Therefore, post-transcriptional modulation could be a potential crucial way to ameliorate skeletal muscle aging after whey protein supplementation. The selected ncRNAs-associated ceRNA networks may provide new insight for the underlying mechanism and profound therapeutic target for skeletal muscle aging., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Emerging evidence highlights the multifunctional role of noncoding RNAs (ncRNAs) in gastric cancer (GC) chemoresistance. However, the comprehensive expression profile and competing endogenous RNAs (ceRNAs) regulatory network of GC chemoresistance remain unanswered., Methods: The whole-transcriptome sequencing (RNA sequencing) was performed to comprehensively analyze the differentially expressed (DE) lncRNAs, miRNAs and mRNAs in cisplatin-resistant cells MGC-803/DDP and GC cells MGC-803. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to investigate the biological functions implicated with the DEncRNAs. Then, the cisplatin-resistant-related ceRNA network and potential regulatory axes were constructed by bioinformatic analysis., Results: We successfully generated cisplatin-resistant GC cell line MGC-803/DDP. Differential expression analysis showed that a total of 1936 DElncRNAs, 2194 DEmRNAs and 174 DEmiRNAs were identified. Functional enrichment analysis indicated that those DEncRNAs were mainly involved in neuroactive ligand-receptor interaction, drug metabolism and Hippo signaling pathway. Subsequently, the cisplatin-resistant-related ceRNA network was constructed with the widely accepted vital chemo-resistant-related genes and signaling pathways. In addition, two constructed regulatory axes (include FAM66C/miR-129-5p/7 mRNAs and SFTA1P/miR-206/FN1 or NRP1) were successfully validated by the Genomic Data Commons (GDC) GC data., Conclusions: The novel ceRNA network and the potential regulatory axes may provide the most comprehensive view of GC chemoresistance to date. Our findings uncovered potential biomarkers for prognostic prediction and novel therapeutic targets for reversing cisplatin resistance in GC., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Non-coding RNA (ncRNA) regulatory networks are emerging as critical regulators of gene expression. These intricate networks of ncRNA:ncRNA interactions modulate multiple cellular pathways and impact the development and progression of multiple diseases. Herpesviruses, including Kaposi's sarcoma-associated herpesvirus, are adept at utilising ncRNAs, encoding their own as well as dysregulating host ncRNAs to modulate virus gene expression and the host response to infection. Research has mainly focused on unidirectional ncRNA-mediated regulation of target protein-coding transcripts; however, we identify a novel host ncRNA regulatory network essential for KSHV lytic replication in B cells. KSHV-mediated upregulation of the host cell circRNA, circHIPK3, is a key component of this network, functioning as a competing endogenous RNA of miR-30c, leading to increased levels of the miR-30c target, DLL4. Dysregulation of this network highlights a novel mechanism of cell cycle control during KSHV lytic replication in B cells. Importantly, disruption at any point within this novel ncRNA regulatory network has a detrimental effect on KSHV lytic replication, highlighting the essential nature of this network and potential for therapeutic intervention., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Osteoarthritis (OA), often called as "wear and tear" arthritis, is the most common form of degenerative joint arthritis and is a leading cause of disability. The nuclear factor-kappaB (NF-κB) transcription factor has long been recognized as a disease-contributing factor for OA. More and more evidences show that targeting NF-κB signaling could offer novel potential therapeutic options for OA damage and reduce the risk of potential side-effects. In recent years, it has been shown that non-coding RNAs(ncRNAs) can trigger the expression of an array of genes and widely activate NF-κB signaling pathway, which induces destruction of the articular joint, leading to OA onset and progression. In this review, we discuss the involvement of NF-κB in OA pathogenesis and how ncRNAs attend and affect OA incidence and evolution, offering novel potential therapeutic options for OA treatment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Osteoblast differentiation is an important process in skeletal development and bone remodelling. Serious bone diseases occur from any delay, defect, or imbalance in osteoblastic differentiation. Non-coding RNAs (ncRNAs) play a regulatory role in controlling the expression of proteins under physiological and pathological conditions via inhibiting mRNA translation or degrading mRNA. Circular RNAs (circRNAs) and microRNAs (miRNAs) are the long and small ncRNAs, respectively, which have been reported to regulate the expression of osteoblast marker genes directly or indirectly. Also, recent studies identified the regulatory mechanisms involving the crosstalk among circRNAs, miRNAs, and mRNAs during osteoblast differentiation. Understanding these regulatory mechanisms behind osteoblastic differentiation would help to diagnose or treat bone and bone-related disorders. Hence, the current review comprehensively discussed the regulatory relationship of circRNAs, miRNAs and mRNAs, and their functional role as circRNA-miRNA-mRNA axis in osteoblast differentiation., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2021 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Inflammation is a multifactorial process and various biological mechanisms and pathways participate in its development. The presence of inflammation is involved in pathogenesis of different diseases such as diabetes mellitus, cardiovascular diseases and even, cancer. Non-coding RNAs (ncRNAs) comprise large part of transcribed genome and their critical function in physiological and pathological conditions has been confirmed. The present review focuses on miRNAs, lncRNAs and circRNAs as ncRNAs and their potential functions in inflammation regulation and resolution. Pro-inflammatory and anti-inflammatory factors are regulated by miRNAs via binding to 3'-UTR or indirectly via affecting other pathways such as SIRT1 and NF-κB. LncRNAs display a similar function and they can also affect miRNAs via sponging in regulating levels of cytokines. CircRNAs mainly affect miRNAs and reduce their expression in regulating cytokine levels. Notably, exosomal ncRNAs have shown capacity in inflammation resolution. In addition to pre-clinical studies, clinical trials have examined role of ncRNAs in inflammation-mediated disease pathogenesis and cytokine regulation. The therapeutic targeting of ncRNAs using drugs and nucleic acids have been analyzed to reduce inflammation in disease therapy. Therefore, ncRNAs can serve as diagnostic, prognostic and therapeutic targets in inflammation-related diseases in pre-clinical and clinical backgrounds., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In eukaryotic organisms such as humans, some noncoding single-stranded RNAs (ncRNAs) contribute to regulating the expression of some genes before and after the transcription process, which in turn controls a number of vital physiological processes, including cell proliferation, differentiation, invasion, angiogenesis, and embryonic development. miR-126 is one of these miRNAs expressed exclusively in endothelial cells such as capillaries and vessels involved in controlling angiogenesis. In recent years, the link between miRs such as miR-126 and the pathology of breast cancer has attracted the attention of many researchers. Numerous studies have shown that miR-126 may be able to suppress tumor tissue metastasis or to increase tumor metastasis through complex molecular mechanisms. There is ample clinical evidence that miR-126 can be used as a biomarker to predict and diagnose breast cancer due to the increased or decreased expression of certain genes in breast cancer tissue. In this review, we discuss the association between the growth and metastasis (tumorigenesis) of breast cancer and miR-126, as well as the relationship between current research advances in the prognosis, diagnosis, and treatment of breast cancer and miR-126., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Biological fluids such as blood, saliva, and urine offer a rich source of biomarkers that have the potential to change the paradigm of cancer management. By allowing routine noninvasive sampling that can offer new insights into cancer progression and response to treatment so-called liquid biopsies can play an important role in personalized medicine. MicroRNAs (miRNAs) are a particularly attractive class of biomarkers as they are not only resistant to the high levels of RNases found in biological fluids, but also able to confer clinically useful information about the disease relating to diagnosis, prognosis, and the response to treatment. Circulating miRNAs are either associated with proteins or extracellular vesicles (EV) and although their origin and implied functions as intracellular messengers remain somewhat controversial, they are implicated in the progression and the establishment of metastatic niches. In this chapter, we review the rapidly emerging field of circulating miRNA cancer biomarkers, their origin and function, techniques to detect these molecules, and the use of bioinformatic tools to derive implied regulatory function, as well as the challenges that lie ahead for their clinical implementation., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)