The regulatory roles of small nucleolar RNAs within their host locus.

Small nucleolar RNAs (snoRNAs) are a class of conserved noncoding RNAs forming complexes with proteins to catalyse site-specific modifications on ribosomal RNA. Besides this canonical role, several snoRNAs are now known to regulate diverse levels of gene expression. While these functions are carried out in trans by mature snoRNAs, evidence has also been emerging of regulatory roles of snoRNAs in cis, either within their genomic locus or as longer transcription intermediates during their maturation. Herein, we review recent findings that snoRNAs can interact in cis with their intron to regulate the expression of their host gene. We also explore the ever-growing diversity of longer host-derived snoRNA extensions and their functional impact across the transcriptome. Finally, we discuss the role of snoRNA duplications into forging these new layers of snoRNA-mediated regulation, as well as their involvement in the genomic imprinting of their host locus.

Noncoding RNAs in skeletal development and disorders.

Protein-encoding genes only constitute less than 2% of total human genomic sequences, and 98% of genetic information was previously referred to as "junk DNA". Meanwhile, non-coding RNAs (ncRNAs) consist of approximately 60% of the transcriptional output of human cells. Thousands of ncRNAs have been identified in recent decades, and their essential roles in the regulation of gene expression in diverse cellular pathways associated with fundamental cell processes, including proliferation, differentiation, apoptosis, and metabolism, have been extensively investigated. Furthermore, the gene regulation networks they form modulate gene expression in normal development and under pathological conditions. In this review, we integrate current information about the classification, biogenesis, and function of ncRNAs and how these ncRNAs support skeletal development through their regulation of critical genes and signaling pathways in vivo. We also summarize the updated knowledge of ncRNAs involved in common skeletal diseases and disorders, including but not limited to osteoporosis, osteoarthritis, rheumatoid arthritis, scoliosis, and intervertebral disc degeneration, by highlighting their roles established from in vivo, in vitro, and ex vivo studies.

Exploring ncRNA-mediated regulation of EGFR signalling in glioblastoma: From mechanisms to therapeutics.

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.

[Research progress of non-coding RNA involved in glycolysis regulation of hepatocellular carcinoma].

Liver cancer is a common tumor of digestive system. Hepatocellular carcinoma (HCC) is a common type of liver cancer, which has a high degree of malignancy and ranks among the top causes of cancer-related death in the world. Metabolic reprogramming is considered to be an important marker of carcinogenesis. Glucose metabolism is one of the main ways for cells to produce energy. Glycolysis, as the basic reaction of glucose metabolism, plays an important role in cell metabolism. Therefore, the regulation of glycolysis is of great significance to the proliferation and evolution of tumors. More and more non-coding RNAs (ncRNA) have been proved to play an important role in the regulation of tumor glycolysis. This article reviews the role of ncRNA in the regulation of HCC glycolysis and its related mechanisms. At the same time, the prospect of targeted therapy for HCC based on the related mechanisms of glycolysis regulation is put forward.

Non-Coding RNA-Targeted Therapy: A State-of-the-Art Review.

The use of non-coding RNAs (ncRNAs) as drug targets is being researched due to their discovery and their role in disease. Targeting ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), is an attractive approach for treating various diseases, such as cardiovascular disease and cancer. This seminar discusses the current status of ncRNAs as therapeutic targets in different pathological conditions. Regarding miRNA-based drugs, this approach has made significant progress in preclinical and clinical testing for cardiovascular diseases, where the limitations of conventional pharmacotherapy are evident. The challenges of miRNA-based drugs, including specificity, delivery, and tolerability, will be discussed. New approaches to improve their success will be explored. Furthermore, it extensively discusses the potential development of targeted therapies for cardiovascular disease. Finally, this document reports on the recent advances in identifying and characterizing microRNAs, manipulating them, and translating them into clinical applications. It also addresses the challenges and perspectives towards clinical application.

The relationship between the network of non-coding RNAs-molecular targets and N6-methyladenosine modification in tumors of urinary system.

N6-methyladenosine (m6A) methylation, a prevalent eukaryotic post-transcriptional modification, is involved in multiple biological functions, including mediating variable splicing, RNA maturation, transcription, and nuclear export, and also is vital for regulating RNA translation, stability, and cytoplasmic degradation. For example, m6A methylation can regulate pre-miRNA expression by affecting both splicing and maturation. Non-coding RNA (ncRNA), which includes microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), does not encode proteins but has powerful impacts on transcription and translation. Conversely, ncRNAs may impact m6A methylation by affecting the expression of m6A regulators, including miRNAs targeting mRNA of m6A regulators, or lncRNAs, and circRNAs, acting as scaffolds to regulate transcription of m6A regulatory factors. Dysregulation of m6A methylation is common in urinary tumors, and the regulatory role of ncRNAs is also important for these malignancies. This article provides a systematic review of the role and mechanisms of action of m6A methylation and ncRNAs in urinary tumors.

Extracellular vesicles as carriers for noncoding RNA-based regulation of macrophage/microglia polarization: an emerging candidate regulator for lung and traumatic brain injuries.

Macrophage/microglia function as immune defense and homeostatic cells that originate from bone marrow progenitor cells. Macrophage/microglia activation is historically divided into proinflammatory M1 or anti-inflammatory M2 states based on intracellular dynamics and protein production. The polarization of macrophages/microglia involves a pivotal impact in modulating the development of inflammatory disorders, namely lung and traumatic brain injuries. Recent evidence indicates shared signaling pathways in lung and traumatic brain injuries, regulated through non-coding RNAs (ncRNAs) loaded into extracellular vesicles (EVs). This packaging protects ncRNAs from degradation. These vesicles are subcellular components released through a paracellular mechanism, constituting a group of nanoparticles that involve exosomes, microvesicles, and apoptotic bodies. EVs are characterized by a double-layered membrane and are abound with proteins, nucleic acids, and other bioactive compounds. ncRNAs are RNA molecules with functional roles, despite their absence of coding capacity. They actively participate in the regulation of mRNA expression and function through various mechanisms. Recent studies pointed out that selective packaging of ncRNAs into EVs plays a role in modulating distinct facets of macrophage/microglia polarization, under conditions of lung and traumatic brain injuries. This study will explore the latest findings regarding the role of EVs in the progression of lung and traumatic brain injuries, with a specific focus on the involvement of ncRNAs within these vesicles. The conclusion of this review will emphasize the clinical opportunities presented by EV-ncRNAs, underscoring their potential functions as both biomarkers and targets for therapeutic interventions.

Deciphering chemoresistance in osteosarcoma: Unveiling regulatory mechanisms and function through the lens of noncoding RNA.

Osteosarcoma (OS) is a primary malignant bone tumor and is prevalent in children, adolescents, and elderly individuals. It has the characteristics of high invasion and metastasis. Neoadjuvant chemotherapy combined with surgical resection is the most commonly used treatment for OS. However, the efficacy of OS is considerably diminished by chemotherapy resistance. In recent years, noncoding RNAs (ncRNAs), including microRNAs, long noncoding RNAs, and circular RNAs, are hot topics in the field of chemotherapy resistance research. Several studies have demonstrated that ncRNAs are substantially associated with chemoresistance in OS. Thus, the present study overviews the abnormally expressed ncRNAs in OS and the molecular mechanisms involved in chemoresistance, with an emphasis on their function in promoting or inhibiting chemoresistance. ncRNAs are expected to become potential therapeutic targets for overcoming drug resistance and predictive biomarkers in OS, which are of great significance for enhancing the therapeutic effect and improving the prognosis.

Imaging and Assay of the Dynamics of Cytotoxic Huntingtin (HTT) Protein Aggregates Regulated by lncRNAs.

Huntington's disease (HD) pathogenesis involves deregulation of coding and noncoding RNA transcripts of which the involvement of long noncoding RNAs (lncRNA) has been realized recently. Of these, Meg3, Neat1, and Xist showed a consistent and significant increase in HD cell and animal models. In the present study, we formulate a methodology to visualize and quantify intracellular aggregates formed by mutant HTT protein. This method employs the use of both confocal laser scanning and super resolution (N-SIM) microscopy to accurately estimate aggregate numbers. Further, to determine the role of two lncRNAs Meg3 and Neat1 in the formation of aggregates of mutant HTT, we used commercially available siRNAs against Meg3 and Neat1 for transiently knocking them down in mouse Neuro2a and human SHSY5Y cells. Co-transfection of 83Q-DsRed and siRNA specific for Neat1 or Meg3 resulted in decreased intracellular aggregates of 83Q-DsRed in both the cell lines. We have established a quantitative method to estimate and directly or indirectly modulate the formation of mutant HTT aggregates.

Regulatory RNAs in immunosenescence.

BACKGROUND: Immunosenescence is a multifactorial stress response to different intrinsic and extrinsic insults that cause immune deterioration and is accompanied by genomic or epigenomic perturbations. It is now widely recognized that genes and proteins contributing in the process of immunosenescence are regulated by various noncoding (nc) RNAs, including microRNAs (miRNAs), long ncRNAs, and circular RNAs. AIMS: This review article aimed to evaluate the regulatore RNAs roles in the process of immunosenescence. METHODS: We analyzed publications that were focusing on the different roles of regulatory RNAs on the several aspects of immunosenescence. RESULTS: In the immunosenescence setting, ncRNAs have been found to play regulatory roles at both transcriptional and post-transcriptional levels. These factors cooperate to regulate the initiation of gene expression programs and sustaining the senescence phenotype and proinflammatory responses. CONCLUSION: Immunosenescence is a complex process with pivotal alterations in immune function occurring with age. The extensive network that drive immunosenescence-related features are are mainly directed by a variety of regulatory RNAs such as miRNAs, lncRNAs, and circRNAs. Latest findings about regulation of senescence by ncRNAs in the innate and adaptive immune cells as well as their role in the immunosenescence pathways, provide a better understanding of regulatory RNAs function in the process of immunosenescence.

Empowering Graph Neural Networks with Block-Based Dual Adaptive Deep Adjustment for Drug Resistance-Related NcRNA Discovery.

Drug resistance to chemotherapeutic agents remains a formidable challenge in cancer treatment, significantly impacting treatment efficacy. Extensive research has exposed the intimate involvement of noncoding RNAs (ncRNAs) in conferring resistance to cancer drugs. Understanding the intricate associations between ncRNAs and drug resistance is of pivotal importance in advancing clinical interventions and expediting drug development. However, traditional biological experimental methods are hampered by limitations, such as labor intensiveness, time consumption, and constraints in scalability. Addressing these challenges necessitates the development of efficient computational methods for the accurate prediction of potential ncRNA-drug resistance associations (NDRA). However, most existing predictive models primarily focus on known ncRNA-drug resistance associations, often neglecting the critical aspect of similarity information between ncRNAs and drug resistance. This oversight may hinder the accuracy of characterizing these associations. To overcome the limitations of existing computational models, we proposed B-NDRA, a computational framework designed for the discovery of drug resistance-related ncRNA. Initially, we constructed a heterogeneous graph that integrates ncRNA-drug resistance pairs, leveraging both known associations and similarity fusion information between ncRNAs and drug resistance. Subsequently, we employed an attention mechanism to aggregate local features of graph nodes following a dimensionality reduction of node features. Further, a graph neural network (GNN) facilitated the learning of global node embeddings. Notably, the integration of dual adaptive deep adjustment architectures, encompassing intrablock and interblock methodologies, enabled efficient extraction of global features while balancing local and global features. Finally, B-NDRA employed a multilayer perceptron to predict associations between ncRNAs and drug resistance. Through rigorous 5-fold cross-validation, B-NDRA achieved average AUC, AUPR, Accuracy, Precision, Recall, and F1-score values of 92.2%, 91.9%, 84.88%, 86.9%, 82.37%, and 84.44%, respectively. Furthermore, comparative evaluations were conducted on established models, namely, GAEMDA, GRPAMDA, and LRGCPND. The results, obtained through three distinct 5-fold cross-validation strategies, demonstrated a notable performance improvement across almost all metrics for our B-NDRA. Specific case studies targeting Doxorubicin and Imatinib further validated the practicality of our B-NDRA in discovering potential NDRA. These results confirm the potential of our B-NDRA as a valuable tool in advancing cancer research and therapeutic development. The source code and data set of B-NDRA can be found at https://github.com/XuanLi1145/B-NDRA.

2'-O-methylation (Nm) in RNA: progress, challenges, and future directions.

RNA 2'-O-methylation (Nm) is highly abundant in noncoding RNAs including ribosomal RNA (rRNA), transfer RNA (tRNA), and small nuclear RNA (snRNA), and occurs in the 5' cap of virtually all messenger RNAs (mRNAs) in higher eukaryotes. More recently, Nm has also been reported to occur at internal sites in mRNA. High-throughput methods have been developed for the transcriptome-wide detection of Nm. However, these methods have mostly been applied to abundant RNAs such as rRNA, and the validity of the internal mRNA Nm sites detected with these approaches remains controversial. Nonetheless, Nm in both coding and noncoding RNAs has been demonstrated to impact cellular processes, including translation and splicing. In addition, Nm modifications at the 5' cap and possibly at internal sites in mRNA serve to prevent the binding of nucleic acid sensors, thus preventing the activation of the innate immune response by self-mRNAs. Finally, Nm has been implicated in a variety of diseases including cancer, cardiovascular diseases, and neurologic syndromes. In this review, we discuss current challenges in determining the distribution, regulation, function, and disease relevance of Nm, as well as potential future directions for the field.

Crosstalk between ubiquitin ligases and ncRNAs drives cardiovascular disease progression.

Cardiovascular diseases (CVDs) are multifactorial chronic diseases and have the highest rates of morbidity and mortality worldwide. The ubiquitin-proteasome system (UPS) plays a crucial role in posttranslational modification and quality control of proteins, maintaining intracellular homeostasis via degradation of misfolded, short-lived, or nonfunctional regulatory proteins. Noncoding RNAs (ncRNAs, such as microRNAs, long noncoding RNAs, circular RNAs and small interfering RNAs) serve as epigenetic factors and directly or indirectly participate in various physiological and pathological processes. NcRNAs that regulate ubiquitination or are regulated by the UPS are involved in the execution of target protein stability. The cross-linked relationship between the UPS, ncRNAs and CVDs has drawn researchers' attention. Herein, we provide an update on recent developments and perspectives on how the crosstalk of the UPS and ncRNAs affects the pathological mechanisms of CVDs, particularly myocardial ischemia/reperfusion injury, myocardial infarction, cardiomyopathy, heart failure, atherosclerosis, hypertension, and ischemic stroke. In addition, we further envision that RNA interference or ncRNA mimics or inhibitors targeting the UPS can potentially be used as therapeutic tools and strategies.

A bibliometric analysis of non-coding RNA studies in acute pancreatitis.

BACKGROUND: Non-coding RNA (ncRNA) is a type of RNA that does not code for proteins and plays a crucial role in the onset, progression, diagnosis, and therapy of acute pancreatitis. However, bibliometric, and visual analyses of studies on acute pancreatitis and ncRNA are lacking. This study seeks to provide a bibliometric overview of the knowledge structure and research hotspots of ncRNA in the field of acute pancreatitis research. MATERIALS AND METHODS: Literature search and collection of information in the field of ncRNA-related research in acute pancreatitis from 2000-2023 through the Web of Science Core Collection. Use CiteSpace and VOSviewer to visually analyze countries, institutions, authors, and keywords. RESULTS: A total of 563 articles have been published in the field of ncRNA-related research in acute pancreatitis, and the number of publications in this field is gradually increasing. The largest number of publications was from China. Four clusters were produced by the co-occurrence cluster analysis of the top 89 keywords: studies of ncRNA in inflammation, autophagy, and apoptosis in acute pancreatitis; studies related to microRNA expression in pancreatic cancer among ncRNA; studies related to microRNAs as diagnostic and therapeutic markers in acute pancreatitis; and studies related to ncRNA in acute pancreatitis; The key words "injury," "pathway" and "extracellular vesicles" are the key words of emerging research hotspots. CONCLUSION: In conclusion, ncRNA research in acute pancreatitis is an established discipline. Researchers can use the research hotspots and frontiers in this field as a guide for choosing their research direction.

Noncoding RNAs as therapeutic targets in autophagy-related diabetic cardiomyopathy.

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.

Exploring ncRNA-mediated pathways in sepsis-induced pyroptosis.

Sepsis, a potentially fatal illness caused by an improper host response to infection, remains a serious problem in the world of healthcare. In recent years, the role of ncRNA has emerged as a pivotal aspect in the intricate landscape of cellular regulation. The exploration of ncRNA-mediated regulatory networks reveals their profound influence on key molecular pathways orchestrating pyroptotic responses during septic conditions. Through a comprehensive analysis of current literature, we navigate the diverse classes of ncRNAs, including miRNAs, lncRNAs, and circRNAs, elucidating their roles as both facilitators and inhibitors in the modulation of pyroptotic processes. Furthermore, we highlight the potential diagnostic and therapeutic implications of targeting these ncRNAs in the context of sepsis, aiming to cover the method for novel and effective strategies to mitigate the devastating consequences of septic pathogenesis. As we unravel the complexities of this regulatory axis, a deeper understanding of the intricate crosstalk between ncRNAs and pyroptosis emerges, offering promising avenues for advancing our approach to sepsis intervention. The intricate pathophysiology of sepsis is examined in this review, which explores the dynamic interaction between ncRNAs and pyroptosis, a highly regulated kind of programmed cell death.

Two effective factors in cancer: Investigating the effect of ncRNAs in cancer and also the effect of nanotherapy in its treatment.

Cancer remains one of the most pressing health challenges globally, necessitating ongoing research into innovative therapeutic approaches. This article explores two critical factors influencing cancer: ncRNAs and nanotherapy. The role of ncRNAs, including microRNAs and long non-coding RNAs, in cancer pathogenesis, progression, and treatment resistance is elucidated. Additionally, the potential of nanotherapy, leveraging nanoscale materials for targeted drug delivery and enhanced therapeutic efficacy, is investigated. By comprehensively analyzing the molecular mechanisms underlying ncRNA dysregulation and the promise of nanotherapy in cancer treatment, this article aims to provide valuable insights into novel therapeutic strategies for combating cancer.

Critical role of exosome, exosomal non-coding RNAs and non-coding RNAs in head and neck cancer angiogenesis.

Head and neck cancer (HNC) refers to the epithelial malignancies of the upper aerodigestive tract. HNCs have a constant yet slow-growing rate with an unsatisfactory overall survival rate globally. The development of new blood vessels from existing blood conduits is regarded as angiogenesis, which is implicated in the growth, progression, and metastasis of cancer. Aberrant angiogenesis is a known contributor to human cancer progression. Representing a promising therapeutic target, the blockade of angiogenesis aids in the reduction of the tumor cells oxygen and nutrient supplies. Despite the promise, the association of existing anti-angiogenic approaches with severe side effects, elevated cancer regrowth rates, and limited survival advantages is incontrovertible. Exosomes appear to have an essential contribution to the support of vascular proliferation, the regulation of tumor growth, tumor invasion, and metastasis, as they are a key mediator of information transfer between cells. In the exocrine region, various types of noncoding RNAs (ncRNAs) identified to be enriched and stable and contribute to the occurrence and progression of cancer. Mounting evidence suggest that exosome-derived ncRNAs are implicated in tumor angiogenesis. In this review, the characteristics of angiogenesis, particularly in HNC, and the impact of ncRNAs on HNC angiogenesis will be outlined. Besides, we aim to provide an insight on the regulatory role of exosomes and exosome-derived ncRNAs in angiogenesis in different types of HNC.