Inflammatory Bowel Disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), is a group of chronic relapsing inflammatory disorders of the gastrointestinal tract with complex etiology and significant clinical challenges. Extracellular vesicles (EVs) act as key mediators of intercellular communication, carrying diverse RNA species—especially non-coding RNAs such as microRNAs and long non-coding RNAs—which have emerged as critical regulators in IBD pathogenesis and progression. This review synthesizes current understanding of how EV-associated RNAs modulate fundamental IBD-related processes, including inflammatory signaling, intestinal barrier function, immune regulation, and host–microbiota interactions. By integrating recent evidence from multi-omics studies and animal models, we highlight the promise of EV-derived RNAs as novel biomarkers and therapeutic targets. We further discuss advances in EV-RNA-based therapeutics and examine the challenges and future directions for translating these insights into clinical practice. By elucidating the multifaceted roles of EV-RNAs in IBD, this article aims to provide a theoretical foundation and inform future research toward precision diagnosis and personalized treatment strategies for IBD patients.
Kirsten RAS viral oncogene homolog (KRAS) is one of the most frequently mutated oncogenes in human cancers. Its mutations result in constitutive activation of the protein, which drives the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling pathways and promotes tumor progression. Meanwhile, microRNAs (miRNAs), as key post-transcriptional regulators, can directly or indirectly modulate the activity of the KRAS signaling network, forming a bidirectional regulatory axis. This review summarizes the complex interplay between KRAS and miRNAs: on one hand, specific miRNAs suppress oncogenic signaling by targeting KRAS or its upstream/downstream effectors; on the other hand, mutant KRAS actively hijacks miRNA biogenesis, processing, and function, leading to a global reprogramming of miRNA expression that drives tumor progression, immune evasion, and drug resistance. In-depth dissection of this dynamic regulatory mechanism not only offers novel insights into the biology of KRAS-driven tumors, but also establishes a theoretical foundation for developing miRNA-based therapeutic interventions.
Recent years have brought the groundbreaking discovery of trained innate immunity, characterized by enhanced monocyte, macrophage and NK cell microbicidal activity. A functional shift of the involved cells results from metabolic rewiring and epigenetic modifications that, among others, are driven by long non-coding ribonucleic acid (lncRNA)-induced effects. However, many questions remain unanswered regarding the precise molecular pathways that ensure trained immunity. In this Commentary article, we aimed to present a comprehensive summary of the key findings from a recently published study that identified a role for lncRNA in monocyte training in the context of tuberculosis. Interestingly, this extracellular vesicle-transferred lncRNA has been shown to stabilize clock circadian regulator (CLOCK) mRNA and, in turn, augment its translation. Consequently, CLOCK-induced histone acetylation upregulates the expression of immune and circadian genes in trained monocyte-derived macrophages. These lncRNA-induced effects were demonstrated to increase antimicrobial resistance after immunization with the Bacillus Calmette-Guérin (BCG) vaccine as well as during unrelated infections. These latter features are desirable characteristics of trained immunity.
Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the respiratory system characterized by persistent difficulties of breathing and dyspnea. COPD patients display emphysema, the anatomic destruction of lung parenchyma accompanied with a high risk for cardiovascular disease, lung cancer, and mortality. The disease is not treatable. Therefore, identifying blood-based biomarkers of COPD, such as non-coding RNAs (ncRNAs), may facilitate early diagnosis, understanding of the molecular basis of COPD and advancement of development of targeted therapies. There is accumulating evidence that dysregulation of ncRNAs plays a crucial role in a variety of diseases, including COPD. The current review gives an overview on extracellular ncRNAs, with a particular focus on microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circularRNAs (circRNAs) in plasma and serum of COPD patients. In addition, the potential role of exosomes carrying ncRNAs from cells to cell in the pathogenesis of COPD is also discussed. Furthermore, the characteristics of these ncRNAs along with their interplay among each other are additionally considered.
Extracellular vesicles of which exosome belong are packet of microRNAs, particular interest the muscle-derived, which are critical regulators of intercellular communication in response to exercise. Strength training modifies muscle physiology and influences the expression and release of a class of microRNA called myomiRs that mediate systemic adaptations. Aim: This review aims to explore the relationship between strength training and skeletal muscle-derived extracellular vesicles–miRNAs. Methods: A comprehensive literature review was conducted, focusing on studies examining the expression, packaging, and function of myomiRs in response to strength training in both human and animal models. Key Findings: Strength training influences the expression and extracellular vesicle-mediated release of myomiRs. These myomiRs may regulate muscle hypertrophy, regeneration, and extracellular signaling. However, most available data remain correlational and not causal. Significance: Understanding the regulation and the systemic role of EVs-microRNA in response to strength training uncovers two aspects: first, the identification of novel biomarkers for the validity of the strength training, and second, the identification of a therapeutic strategy for musculoskeletal health.
Cancer remains a leading cause of mortality worldwide despite the development of novel, precise, and less invasive strategies for diagnosis, prognosis, and treatment. Encapsulated within different extracellular vesicles (EVs), especially exosomes, extracellular RNAs (exRNAs) have become important players in disease pathogenesis and intercellular communication. They are perfect candidates for liquid biopsies because of their stability, ubiquity in biofluids, and capacity to replicate the physiological and pathological conditions of parental cells. The growing role of exRNAs as “theranostic agents” in cancer, combining diagnostic, prognostic, and therapeutic capabilities, is thoroughly explored in this review. We investigate their potential as non-invasive biomarkers for tumor classification, early detection, and disease progression or recurrence prediction. Furthermore, we discuss the expanding therapeutic potential of exRNAs, which is frequently made possible by engineered exosome platforms and ranges from delivering therapeutic RNA molecules to inhibiting oncogenic exRNAs. Finally, we also highlight the current challenges in exRNA research, such as targeted delivery, standardization, isolation, and characterization, and we outline potential future directions for integrating exRNA-based theranostics into standard clinical practice for better cancer patient care.
Atherosclerosis remains a major contributor to cardiovascular morbidity and mortality, even with widespread use of lipid-lowering, antihypertensive, and anti-inflammatory therapies. The persistent residual risk and endothelial dysfunction highlight the need for targeted, mechanistically driven interventions. Among emerging regulators, microRNAs (miRNAs) offer precise control over gene networks implicated in atherogenesis. This review focuses on two well-characterized miRNAs with complementary roles: miR-33a/b, which impairs cholesterol efflux by targeting ABCA1 and ABCG1, and miR-92a, which disrupts endothelial homeostasis through suppression of KLF2, KLF4, and endothelial nitric oxide synthase (eNOS). We summarize their roles in key signaling pathways, including insulin and nitric oxide signaling, and examine recent advances in antisense oligonucleotide-based therapeutics and nanoparticle-mediated delivery. Together, these miRNAs represent promising precision targets for restoring lipid balance and vascular integrity, with early clinical trials supporting the translational potential of miRNA-based interventions for cardiovascular disease.
Mesenchymal stem cells (MSCs) are known for their ability to differentiate and self-renew, playing a critical role in tissue homeostasis and repair. Despite their therapeutic potential, clinical applications of MSCs face challenges, including safety concerns and uncertain effects on tumors. In contrast, MSC-derived exosomes (MSC-EXOs) have shown comparable or superior efficacy across various diseases, primarily due to their cargo of functional RNAs and proteins. These natural nanovesicles offer a promising drug delivery platform, combining the advantages of both MSCs and exosomes. Genetic engineering approaches, such as surface modification and drug loading, further enhance their therapeutic capabilities. Small RNA drugs present novel opportunities for expanding therapeutic targets, but efficient delivery remains a significant challenge. MSC-EXOs, either natural or engineered, provide a safe and effective solution for delivering small RNA drugs, holding great promise for both research and translational applications. However, large-scale production of MSC-EXOs remains a key hurdle, and ongoing efforts focus on optimizing strategies for producing high-quality MSC-EXOs in sufficient quantities for industrial and clinical use. This review examines the role of MSC-EXOs in small RNA drug delivery, highlighting the associated challenges and potential solutions for scalable production.
EGFR mutations serve as a pivotal driver in NSCLC, where their aberrant activation promotes tumor proliferation, metastasis, and survival through downstream signaling pathways. Although EGFR-TKIs effectively target mutant EGFR, acquired resistance significantly diminishes their clinical efficacy. Recent studies have demonstrated that ncRNAs play a critical role in the dynamic regulatory network of the EGFR signaling pathway and are deeply implicated in the development of EGFR-TKI resistance in lung cancer. This review focuses on the dynamic bidirectional regulatory mechanisms between ncRNAs and the EGFR signaling pathway, as well as the multifaceted molecular mechanisms through which ncRNAs mediate resistance to EGFR-TKI therapy. Elucidating the interaction network between ncRNAs and the EGFR pathway not only provides novel molecular insights into resistance mechanisms but also establishes a theoretical foundation for developing ncRNA-based combination therapeutic strategies and dynamic biomarkers for monitoring resistance evolution, highlighting significant translational and clinical potential.
Numerous preanalytical variables (sample collection, pretreatment and storage conditions, miRNA extraction, etc.) can influence miRNA detection. Understanding the various properties of miRNA, especially its stability in biofluids, is important in various types of miRNA studies, both fundamental and applied. This study aimed to evaluate the influence of plasma storage conditions and certain RNA extraction parameters on stability of endogenous miRNAs in human blood plasma. We report stability kinetics of four endogenous miRNAs (-16, -19b, -23a, -451a) and cel-miR-39 as exogenous miRNA under short and long-term incubation at different temperatures as well as the effect of long-term storage on extracellular vesicles miRNAs stability. The most stable of the endogenous ones was miRNA-23a. When studying archival samples (1–2 and 9–10 years of storage) of blood plasma from healthy donors, it was shown, that the concentrations of all endogenous miRNAs are steadily decreasing. These findings further show that endogenous miRNA levels do not remain stable during prolonged storage at −20°C. Although packaging of miRNA in extracellular vesicles stabilizes miRNA to some extent, it nevertheless the level decreases over a period of time from 6 months to 6 years. We have also evaluated the effect of the reagents used in the extraction process on miRNA recovery. The addition of guanidine isothiocyanate containing denaturation buffer alone prevented degradation of the synthetic cel-miR-39 miRNA spiked-in to blood plasma. In the presence of denaturation buffer with or without 2-mercaptoethanol the yields were higher than with just 2-mercaptoethanol or in the absence of any agents. Addition of the commercial RNA-stabilizing agent RNAlater did not result in significant retention of miRNA in plasma, but significantly worsened the efficiency of miRNA isolation. Thus, the degradation rate of miRNAs can be affected by their structure and packaging. Addition of various stabilization solutions to biofluids can affect the efficiency of miRNA extraction.
Gutter oil, a major public health concern in East Asia, is often indistinguishable from pure edible oils using conventional physical and chemical methods. In this study, we present a novel approach for detecting gutter oil using microRNAs (miRNAs) as biomarkers. We proved that miRNAs exist in edible oils and can be used to differentiate between pure and recycled oils. A combination of qRT-PCR and machine learning techniques was employed to characterize miRNA profiles across commercial vegetable oils, animal oils, and gutter oil. Specifically, the relative abundances of miR-16 and let-7a were found to be significantly different among these oils, allowing for accurate differentiation via a support vector machine (SVM) model. The results indicate that miRNAs such as miR-16 and let-7a serve as reliable biomarkers, enabling classification of gutter oil even when it complies with national standards. This research provides a feasible and effective method for detecting gutter oil, with potential implications for improving food safety and public health.
RNA, a crucial molecule in protein synthesis and gene expression regulation, plays an essential role in organisms. RNA modifications, acting as epigenetic marks, subtly adjust the structure, stability, and function of RNA, thereby regulating gene expression and exerting profound effects on cellular functions and organismal health. These natural modifications, together with RNA editing that alters nucleotide sequence of mRNA, constitute the epitranscriptome, which is vital for cellular metabolism. With the rapid advancement of biotechnology, RNA-based therapies and technologies have emerged as a frontier in biotech research. Various RNA drugs, including small interfering RNA (siRNA), antisense oligonucleotides (ASO), mRNA vaccines, and the small guide RNA (sgRNA) required for CRISPR gene editing, have been continuously developed. It has been widely demonstrated that RNA modifications can alter the physicochemical properties of RNA, enhance resistance to nucleases, reduce immunogenicity, and optimize in vivo functionality, leading to their extensive application in RNA-related biotechnologies. Furthermore, the variety of RNA modifications has expanded beyond natural modifications with the invention of an increasing number of artificial modifications. This review delves into the common types of RNA modifications, including base, ribose, and phosphate modifications, discussing their impact on RNA structure and how these modifications influence the biological characteristics of RNA. The current applications of these modifications in the biotechnology field are summarized, highlighting their significance in RNA-based therapies.
The polarization of macrophages towards an anti-inflammatory and/or pro-tissue repairing phenotype has shown promising potential in the treatment of ischemic diseases. Macrophages play a crucial role in promoting the growth of new blood vessels in ischemic tissue by clearing apoptotic debris caused by hypoxia, recruiting immune cells that support tissue repair, and releasing a variety of cytokines and growth factors. However, there is still a significant knowledge gap regarding the effective induction of this specific macrophage polarization. Non-coding RNAs have demonstrated promise in regulating macrophage activity, although there is a need for more efficient delivery system. Exosomes, which are cell-derived extracellular vesicles ranging from 30 nm to 200 nm in size, have emerged as promising carriers of non-coding RNAs for regulating macrophage activity. This review will discuss the important role of macrophage polarization in ischemic diseases and explore the potential of non-coding RNAs delivered by exosomes in modulating macrophage polarization.
Head and neck cancers (HNCs) are malignant tumors that differ from carcinomas in their biological behaviour and require a different diagnostic and treatment approach, especially in cancers like lung, breast, and prostate. Exosomal RNA (exRNA), particularly miRNA, mRNA, and lncRNA in blood or other body fluids through liquid biopsy, is emerging as a non-invasive biomarker for early cancer detection, prognosis, and treatment monitoring. Exosomal RNA modulates key signalling pathways like NF-κB, EGFR, PI3K/AKT/mTOR, and TP53 and contributes to the development, progression and therapeutic resistance of cancers. In this review, we focus on the roles of exosomal RNA in the growth and evolution of head and neck squamous cell carcinoma (HNSCC) as well as the emerging therapeutic strategies targeting exosomal RNA to improve clinical outcomes in HNC patients.
Under physiological conditions, the body maintains glucose homeostasis through interorgan communication between metabolic organs. As is well known, this crosstalk is mediated by traditional hormones or metabolites. Recently, a new type of secreted factor called RNAkine has become increasingly prominent in regulating glucose homeostasis. They are secreted non-coding RNAs that are mainly transported from the origin cells to the target cells through extracellular vesicles (EVs), participating in interorgan communication. In this review, we summarized the various organs involved in glucose homeostasis and their inter-organ crosstalk, and emphasized the important role of RNAkines which is of great significance for both the prevention and treatment of type 2 diabetes mellitus (T2DM).
