ncRNA Research Research Articles

Non-coding RNA notations, regulations and interactive resources.

An increasing number of non-coding RNAs (ncRNAs) are found to have roles in gene expression and cellular regulations. However, there are still a large number of ncRNAs whose functions remain to be studied. Despite decades of research, the field continues to evolve, with each newly identified ncRNA undergoing processes such as biogenesis, identification, and functional annotation. Bioinformatics methodologies, alongside traditional biochemical experimental methods, have played an important role in advancing ncRNA research across various stages. Presently, over 50 types of ncRNAs have been characterized, each exhibiting diverse functions. However, there remains a need for standardization and integration of these ncRNAs within a unified framework. In response to this gap, this review traces the historical trajectory of ncRNA research and proposes a unified notation system. Additionally, we comprehensively elucidate the ncRNA interactome, detailing its associations with DNAs, RNAs, proteins, complexes, and chromatin. A web portal named ncRNA Hub ( https://bis.zju.edu.cn/nchub/ ) is also constructed to provide detailed notations of ncRNAs and share a collection of bioinformatics resources. This review aims to provide a broader perspective and standardized paradigm for advancing ncRNA research.

Deciphering the roles of cellular and extracellular non-coding RNAs in chemotherapy-induced cardiotoxicity.

Chemotherapy-induced cardiotoxicity is a major adverse effect, driven by multiple factors in its pathogenesis. Notably, RNAs have emerged as significant contributors in both cancer and heart failure (HF). RNAs carry genetic and metabolic information that mirrors the current state of cells, making them valuable as potential biomarkers and therapeutic tools for diagnosing, predicting, and treating a range of diseases, including cardiotoxicity. Over 97% of the genome is transcribed into non-coding RNAs (ncRNAs), including ribosomal RNA (rRNAs), transfer RNAs (tRNAs), and newly identified microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs). NcRNAs function not only within their originating cells but also in recipient cells by being transported through extracellular compartments, referred to as extracellular RNAs (exRNAs). Since ncRNAs were identified as key regulators of gene expression, numerous studies have highlighted their significance in both cancer and cardiovascular diseases. Nevertheless, the role of ncRNAs in cardiotoxicity remains not fully elucidated. The study aims to review the existing knowledge on ncRNAs in Cardio-Oncology and explore the potential of ncRNA-based biomarkers and therapies. These investigations could advance the clinical application of ncRNA research, improving early detection and mitigating of chemotherapy-induced cardiotoxicity.

Improving ncRNA family prediction using multi-modal contrastive learning of sequence and structure.

Recent advancements in high-throughput sequencing technology have significantly increased the focus on non-coding RNA (ncRNA) research within the life sciences. Despite this, the functions of many ncRNAs remain poorly understood. Research suggests that ncRNAs within the same family typically share similar functions, underlining the importance of understanding their roles. There are two primary methods for predicting ncRNA families: biological and computational. Traditional biological methods are not suitable for large-scale data prediction due to the significant human and resource requirements. Concurrently, most existing computational methods either rely solely on ncRNA sequence data or are exclusively based on the secondary structure of ncRNA molecules. These methods fail to fully utilize the rich multimodal information available from ncRNAs, thereby preventing them from learning more comprehensive and in-depth feature representations. To tackle these problems, we proposed MM-ncRNAFP, a multi-modal contrastive learning framework for ncRNA family prediction. We first used a pre-trained language model to encode the primary sequences of a large mammalian ncRNA dataset. Then, we adopted a contrastive learning framework with an attention mechanism to fuse the secondary structure information obtained by graph neural networks. The MM-ncRNAFP method can effectively fuse multi-modal information. Experimental comparisons with several competitive baselines demonstrated that MM-ncRNAFP can achieve more comprehensive representations of ncRNA features by integrating both sequence and structural information. This integration significantly enhances the performance of ncRNA family prediction. Ablation experiments and qualitative analyses were performed to verify the effectiveness of each component in our model. Moreover, since our model is pre-trained on a large amount of ncRNA data, it has the potential to bring significant improvements to other ncRNA-related tasks. MM-ncRNAFP and the datasets are available at https://github.com/xuruiting2/MM-ncRNAFP.

Circulating small non-coding RNA profiling for identification of older adults with low muscle strength and physical performance: A preliminary study

BackgroundSmall non-coding RNAs (ncRNAs) have recently emerged as potential biomarkers of sarcopenia. However, previous studies have rarely explored the association of small ncRNAs with sarcopenic components, especially muscle strength and physical performance. We aimed to examine circulating small ncRNA profiles to detect low muscle strength and physical performance in older adults. MethodsNinety-eight older adults were randomly selected from Korean Frailty and Aging Cohort Study and classified into the “Normal,” “Low muscle strength (MS) only,” “Low physical performance (PP) only,” and “Low MS and PP” groups by Asian Working Group for Sarcopenia 2019 criteria. We used high-throughput sequencing to delineate small ncRNA profiles in plasma. Differentially expressed small ncRNAs were analyzed to reveal distinct patterns based on muscle strength and physical performance status. ResultsIn “Low MS and PP” group, 119 miRNAs, 86 piRNAs, 92 snoRNAs, 106 snRNAs, and 15 tRNAs were differentially expressed compared to “Normal” group (p < 0.05). After Benjamini-Hochberg adjustment, 39 miRNAs, 2 piRNAs, 75 snoRNAs, 48 snRNAs, and 15 tRNAs showed differential expression in “Low MS and PP” group compared to than “Normal” group (adjusted p < 0.05). No significant differences were observed in comparisons between the other groups (adjusted p > 0.05). ConclusionThe expression of circulating small ncRNAs were comprehensively characterized, revealing distinct signatures in older adults with both low muscle strength and physical performance compared to normal individuals. Although preliminary, this characterization can advance small ncRNA research on age-related declines in muscle strength and physical performance by providing foundational data for further investigation.

Non-Coding RNA as a Biomarker in Lung Cancer.

Lung cancer remains one of the most prevalent and deadly cancers globally, with high mortality rates largely due to late-stage diagnosis, aggressive progression, and frequent recurrence. Despite advancements in diagnostic techniques and therapeutic interventions, the overall prognosis for lung cancer patients continues to be dismal. Emerging research has identified non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, and circular RNAs, as critical regulators of gene expression, significantly influencing cancer biology. These ncRNAs play pivotal roles in various aspects of lung cancer pathogenesis, including tumor initiation, progression, metastasis, and resistance to therapy. We provide a comprehensive analysis of the current understanding of ncRNAs in lung cancer, emphasizing their potential as biomarkers for early diagnosis, prognostication, and the prediction of the therapeutic response. We explore the biological functions of ncRNAs, their involvement in key oncogenic pathways, and the molecular mechanisms by which they modulate gene expression and cellular processes in lung cancer. Furthermore, this review highlights recent advances in ncRNA-based diagnostic tools and therapeutic strategies, such as miRNA mimics and inhibitors, lncRNA-targeted therapies, and circRNA-modulating approaches, offering promising avenues for personalized medicine. Finally, we discuss the challenges and future directions in ncRNA research, including the need for large-scale validation studies and the development of efficient delivery systems for ncRNA-based therapies. This review underscores the potential of ncRNAs to revolutionize lung cancer management by providing novel diagnostic and therapeutic options that could improve patient outcomes.

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

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. 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. 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. 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.

Non-Coding RNA-Mediated Gene Regulation in Cardiovascular Disorders: Current Insights and Future Directions.

Cardiovascular diseases (CVDs) pose a significant burden on global health. Developing effective diagnostic, therapeutic, and prognostic indicators for CVDs is critical. This narrative review explores the role of select non-coding RNAs (ncRNAs) and provides an in-depth exploration of the roles of miRNAs, lncRNAs, and circRNAs in different aspects of CVDs, offering insights into their mechanisms and potential clinical implications. The review also sheds light on the diverse functions of ncRNAs, including their modulation of gene expression, epigenetic modifications, and signaling pathways. It comprehensively analyzes the interplay between ncRNAs and cardiovascular health, paving the way for potential novel interventions. Finally, the review provides insights into the methodologies used to investigate ncRNA-mediated gene regulation in CVDs, as well as the implications and challenges associated with translating ncRNA research into clinical applications. Considering the broader implications, this research opens avenues for interdisciplinary collaborations, enhancing our understanding of CVDs across scientific disciplines.

Role of Actin-Binding Proteins in Skeletal Myogenesis.

Maintenance of skeletal muscle quantity and quality is essential to ensure various vital functions of the body. Muscle homeostasis is regulated by multiple cytoskeletal proteins and myogenic transcriptional programs responding to endogenous and exogenous signals influencing cell structure and function. Since actin is an essential component in cytoskeleton dynamics, actin-binding proteins (ABPs) have been recognized as crucial players in skeletal muscle health and diseases. Hence, dysregulation of ABPs leads to muscle atrophy characterized by loss of mass, strength, quality, and capacity for regeneration. This comprehensive review summarizes the recent studies that have unveiled the role of ABPs in actin cytoskeletal dynamics, with a particular focus on skeletal myogenesis and diseases. This provides insight into the molecular mechanisms that regulate skeletal myogenesis via ABPs as well as research avenues to identify potential therapeutic targets. Moreover, this review explores the implications of non-coding RNAs (ncRNAs) targeting ABPs in skeletal myogenesis and disorders based on recent achievements in ncRNA research. The studies presented here will enhance our understanding of the functional significance of ABPs and mechanotransduction-derived myogenic regulatory mechanisms. Furthermore, revealing how ncRNAs regulate ABPs will allow diverse therapeutic approaches for skeletal muscle disorders to be developed.

Research progress on the regulation of bone marrow stem cells by noncoding RNAs in adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity in young women, but its pathogenesis remains unclear. The primary pathogenic factors contributing to its development include genetics, abnormal bone metabolism, and endocrine factors. Bone marrow stem cells (BMSCs) play a crucial role in the pathogenesis of AIS by regulating its occurrence and progression. Noncoding RNAs (ncRNAs) are also involved in the pathogenesis of AIS, and their role in regulating BMSCs in patients with AIS requires further evaluation. In this review, we discuss the relevant literature regarding the osteogenic, chondrogenic, and lipogenic differentiation of BMSCs. The corresponding mechanisms of ncRNA-mediated BMSC regulation in patients with AIS, recent advancements in AIS and ncRNA research, and the importance of ncRNA translation profiling and multiomics are highlighted.

RNAenrich: a web server for non-coding RNA enrichment.

With the rapid advances of RNA sequencing and microarray technologies in non-coding RNA (ncRNA) research, functional tools that perform enrichment analysis for ncRNAs are needed. On the one hand, because of the rapidly growing interest in circRNAs, snoRNAs, and piRNAs, it is essential to develop tools for enrichment analysis for these newly emerged ncRNAs. On the other hand, due to the key role of ncRNAs' interacting target in the determination of their function, the interactions between ncRNA and its corresponding target should be fully considered in functional enrichment. Based on the ncRNA-mRNA/protein-function strategy, some tools have been developed to functionally analyze a single type of ncRNA (the majority focuses on miRNA); in addition, some tools adopt predicted target data and lead to only low-confidence results. Herein, an online tool named RNAenrich was developed to enable the comprehensive and accurate enrichment analysis of ncRNAs. It is unique in (i) realizing the enrichment analysis for various RNA types in humans and mice, such as miRNA, lncRNA, circRNA, snoRNA, piRNA, and mRNA; (ii) extending the analysis by introducing millions of experimentally validated data of RNA-target interactions as a built-in database; and (iii) providing a comprehensive interacting network among various ncRNAs and targets to facilitate the mechanistic study of ncRNA function. Importantly, RNAenrich led to a more comprehensive and accurate enrichment analysis in a COVID-19-related miRNA case, which was largely attributed to its coverage of comprehensive ncRNA-target interactions. RNAenrich is now freely accessible at https://idrblab.org/rnaenr/.

Noncoding RNAs in asthmatic airway smooth muscle cells.

Asthma is a complex and heterogeneous airway disease caused by genetic, environmental and epigenetic factors treated with hormones and biologics. Irreversible pathological changes to airway smooth muscle cells (ASMCs) such as hyperplasia and hypertrophy can occur in asthmatic patients. Determining the mechanisms responsible is vital for preventing such changes. In recent years, noncoding RNAs (ncRNAs), especially microRNAs, long noncoding RNAs and circular RNAs, have been found to be associated with abnormalities of the ASMCs. This review highlights recent ncRNA research into ASMC pathologies. We present a schematic that illustrates the role of ncRNAs in pathophysiological changes to ASMCs that may be useful in future research in diagnostic and treatment strategies for patients with asthma.

Noncoding RNAs as Key Regulators for Cardiac Development and Cardiovascular Diseases.

Noncoding RNAs (ncRNAs) play fundamental roles in cardiac development and cardiovascular diseases (CVDs), which are a major cause of morbidity and mortality. With advances in RNA sequencing technology, the focus of recent research has transitioned from studies of specific candidates to whole transcriptome analyses. Thanks to these types of studies, new ncRNAs have been identified for their implication in cardiac development and CVDs. In this review, we briefly describe the classification of ncRNAs into microRNAs, long ncRNAs, and circular RNAs. We then discuss their critical roles in cardiac development and CVDs by citing the most up-to-date research articles. More specifically, we summarize the roles of ncRNAs in the formation of the heart tube and cardiac morphogenesis, cardiac mesoderm specification, and embryonic cardiomyocytes and cardiac progenitor cells. We also highlight ncRNAs that have recently emerged as key regulators in CVDs by focusing on six of them. We believe that this review concisely addresses perhaps not all but certainly the major aspects of current progress in ncRNA research in cardiac development and CVDs. Thus, this review would be beneficial for readers to obtain a recent picture of key ncRNAs and their mechanisms of action in cardiac development and CVDs.

MiRNAs and lncRNAs in tomato: Roles in biotic and abiotic stress responses.

Plants are continuously exposed to various biotic and abiotic stresses in the natural environment. To cope with these stresses, they have evolved a multitude of defenses mechanisms. With the rapid development of genome sequencing technologies, a large number of non-coding RNA (ncRNAs) have been identified in tomato, like microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Recently, more and more evidence indicates that many ncRNAs are involved in plant response to biotic and abiotic stresses in tomato. In this review, we summarize recent updates on the regulatory roles of ncRNAs in tomato abiotic/biotic responses, including abiotic (high temperature, drought, cold, salinization, etc.) and biotic (bacteria, fungi, viruses, insects, etc.) stresses. Understanding the molecular mechanisms mediated by ncRNAs in response to these stresses will help us to clarify the future directions for ncRNA research and resistance breeding in tomato.

Computational model for ncRNA research.

The explosion of research on non-coding RNAs (ncRNAs) in the past few decades has transformed the original notion of regarding such RNAs as ‘transcriptional noise’ [1, 2] before 1980s to gene expression regulators at transcriptional, RNA processing and translational levels [3–6]. It is evident from PubMed that each week new studies are published to reveal altered ncRNA expressions in diseases or discover novel non-coding transcripts [7]. Abundant in eukaryotes ranging from Homo sapiens to Caenorhabditis elegans [8, 9] and persistent in prokaryotes such as bacteria [10, 11], ncRNAs fall into two main classes according to transcript length [12, 13]: long ncRNAs (lncRNAs, with length > 200 bp) and small ncRNAs (sncRNAs, with length < 200 bp). Based on conformation and cellular function [14–17], the former can be further divided into linear RNAs and circular RNAs (circRNAs), whereas the latter can be grouped into more than a dozen subclasses, among which microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs) have recently attracted considerable research attention.

Literature Mining of Disease Associated Noncoding RNA in the Omics Era.

Noncoding RNAs (ncRNA) are transcripts without protein-coding potential that play fundamental regulatory roles in diverse cellular processes and diseases. The application of deep sequencing experiments in ncRNA research have generated massive omics datasets, which require rapid examination, interpretation and validation based on exiting knowledge resources. Thus, text-mining methods have been increasingly adapted for automatic extraction of relations between an ncRNA and its target or a disease condition from biomedical literature. These bioinformatics tools can also assist in more complex research, such as database curation of candidate ncRNAs and hypothesis generation with respect to pathophysiological mechanisms. In this concise review, we first introduced basic concepts and workflow of literature mining systems. Then, we compared available bioinformatics tools tailored for ncRNA studies, including the tasks, applicability, and limitations. Their powerful utilities and flexibility are demonstrated by examples in a variety of diseases, such as Alzheimer’s disease, atherosclerosis and cancers. Finally, we outlined several challenges from the viewpoints of both system developers and end users. We concluded that the application of text-mining techniques will booster disease-associated ncRNA discoveries in the biomedical literature and enable integrative biology in the current omics era.

Integrative approaches for studying the role of noncoding RNAs in influencing drug efficacy and toxicity

Introduction Drug efficacy and toxicity are important factors for evaluation in drug development. Drug metabolizing enzymes and transporters (DMETs) play an essential role in drug efficacy and toxicity. Noncoding RNAs (ncRNAs) have been implicated to influence inter-individual variations in drug efficacy and safety by regulating DMETs. An efficient strategy is urgently needed to identify and functionally characterize ncRNAs that mediate drug efficacy and toxicity through regulating DMETs. Areas covered : We outline an integrative strategy to identify ncRNAs that modulate DMETs. We include reliable tools and databases for computational prediction of ncRNA targets with regards to their advantages and limitations. Various biochemical, molecular, and cellular assays are discussed for in vitro experimental verification of the regulatory function of ncRNAs. In vivo approaches for association of ncRNAs with drug treatment and toxicity are also reviewed. Expert opinion : A streamlined integration of computational prediction and wet-lab validation is important to elucidate mechanisms of ncRNAs in the regulation of DMETs related to drug efficacy and safety. Bioinformatic analyses using open-access tools and databases serve as a powerful booster for ncRNA research in toxicology. Further refinement of computational algorithms and experimental technologies is needed to improve accuracy and efficiency in ncRNA target identification and characterization.

Highlights from the ‘Noncoding RNA world: From Mechanism to Therapy’ conference, July 21-23, 2021

Non‑coding RNAs (ncRNAs) are involved in different cellular processes and some of them are considered to play a role in the development of numerous diseases. The recent discovery of ncRNAs is the result of several experimental and bioinformatics studies. On July 21‑23, 2021, the ‘Noncoding RNA World: From Mechanism to Therapy’ conference that was held virtually (originally planned to be held in Basel, Switzerland), gathered experts and researchers from countries worldwide to cover the latest achievements in ncRNA research, including the basic molecular mechanisms and structural biology, bioinformatics, biotechnology, disease development and therapeutics of ncRNAs. The meeting was dominated by a feeling of satisfaction and enthusiasm for the novel discoveries in the ncRNA field that is considered to be relatively new. Intriguingly, several discoveries are added daily beside numerous hurdles that are encountered or remain to be resolved in order for these findings to be translated into clinical practice.

Elucidating the Functions of Non-Coding RNAs from the Perspective of RNA Modifications

It is now commonly accepted that most of the mammalian genome is transcribed as RNA, yet less than 2% of such RNA encode for proteins. A majority of transcribed RNA exists as non-protein-coding RNAs (ncRNAs) with various functions. Because of the lack of sequence homologies among most ncRNAs species, it is difficult to infer the potential functions of ncRNAs by examining sequence patterns, such as catalytic domains, as in the case of proteins. Added to the existing complexity of predicting the functions of the ever-growing number of ncRNAs, increasing evidence suggests that various enzymes modify ncRNAs (e.g., ADARs, METTL3, and METTL14), which has opened up a new field of study called epitranscriptomics. Here, we examine the current status of ncRNA research from the perspective of epitranscriptomics.

In vivo fermentation production of humanized noncoding RNAs carrying payload miRNAs for targeted anticancer therapy.

Rationale: Noncoding RNAs (ncRNAs) such as microRNAs (miRs or miRNAs) play important roles in the control of cellular processes through posttranscriptional gene regulation. However, ncRNA research is limited to utilizing RNA agents synthesized in vitro. Recombinant RNAs produced and folded in living cells shall better recapitulate biologic RNAs.Methods: Herein, we developed a novel platform for in vivo fermentation production of humanized recombinant ncRNA molecules, namely hBERAs, carrying payload miRNAs or siRNAs. Target hBERAs were purified by anion exchange FPLC method. Functions of hBERA/miRNAs were investigated in human carcinoma cells and antitumor activities were determined in orthotopic osteosarcoma xenograft spontaneous lung metastasis mouse models.Results: Proper human tRNAs were identified to couple with optimal hsa-pre-miR-34a as new fully-humanized ncRNA carriers to accommodate warhead miRNAs or siRNAs. A group of 30 target hBERAs were all heterogeneously overexpressed (each accounting for >40% of total bacterial RNA), which facilitated large-scale production (8-31 mg of individual hBERAs from 1L bacterial culture). Model hBERA/miR-34a-5p and miR-124-3p were selectively processed to warhead miRNAs in human carcinoma cells to modulate target gene expression, enhance apoptosis and inhibit invasiveness. In addition, bioengineered miR-34a-5p and miR-124-3p agents both reduced orthotopic osteosarcoma xenograft tumor growth and spontaneous pulmonary metastases significantly.Conclusion: This novel ncRNA bioengineering technology and resulting recombinant ncRNAs are unique additions to conventional technologies and tools for basic research and drug development.

Non-coding RNAs, guardians of the p53 galaxy.

The TP53 gene is arguably the most important tumor suppressor gene known, contributing multifaceted roles to the process of tumor development. Its protein product p53, is a crucial sequence-specific transcription factor which regulates the expression of a large network of protein-coding genes, as well as thousands of noncoding RNAs (ncRNAs), notably microRNAs and long ncRNAs (lncRNAs). Through a variety of direct and indirect mechanisms, ncRNAs in turn modulate p53 levels and activity. Here the numbers of studies are steadily building which link the contributions of dysregulated ncRNAs to tumorigenesis via their participation throughout the p53 regulatory network. In this review, we will examine how the principal forms of ncRNAs, namely microRNAs, lncRNAs and circular RNAs (circRNAs) function as either effectors or regulators amongst the diversity of p53's cellular responses. We first discuss the more recently discovered connections between miRNAs and p53 signaling before focusing on the remarkable diversity of crosstalk evident between lncRNAs and p53, and subsequently, developing reports linking circRNAs to p53. Highlighted throughout the review are the mechanistic impacts of dysregulated ncRNAs on p53 functions as well as the possible prognostic implications of these interactions. We also describe the emerging connections between ncRNAs and the often-perplexing functions of mutant p53. Finally, in the context of p53 therapeutic approaches, we describe some of the challenges in ncRNA research and their potential for translation.