Search Results (35)

Prostate cancer (PCa) is the most common malignancy in men, characterized by significant genetic and epigenetic heterogeneity, which complicates both diagnosis and treatment processes. Epigenetic mechanisms—including DNA methylation, chromatin remodeling, and dysregulated non-coding RNAs (miRNAs, lncRNAs, circRNAs)—contribute to tumor initiation, progression, and therapy resistance, offering promising diagnostic and prognostic biomarker opportunities. Liquid biopsy technologies, such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomes, allow minimally invasive, real-time monitoring of tumor evolution and resistance mechanisms, complementing traditional biomarkers like PSA and supporting precision oncology approaches. Clinically implemented assays, including PCA3, ConfirmMDx, and ExoDx Prostate, along with emerging multi-analyte panels, enhance risk stratification, reduce unnecessary biopsies, and guide therapeutic decisions. Integration of epigenetic and liquid biopsy biomarkers into multimodal diagnostic pathways has the potential to support personalized management of prostate cancer; however, many still require further validation and optimization. Full article

Carotid atherosclerosis remains one of the primary etiological factors underlying ischemic stroke, contributing to adult neurological disability and mortality. In recent years, non-coding RNAs (ncRNAs) have emerged as key regulators of gene expression, actively modulating molecular pathways involved in atherogenesis. This systematic review, the first to be exclusively focused on carotid atherosclerosis, aimed at synthesizing current findings on the differential expression of ncRNAs throughout the natural history of the disease, thus providing the first comprehensive attempt to delineate a stage-specific ncRNA expression profile in carotid disease. A comprehensive literature search was conducted in PubMed and Scopus databases in January 2025, following PRISMA guidelines. Original studies involving human subjects with carotid atherosclerosis, evaluating the expression of intracellular or circulating ncRNAs, were included and then categorized according to their association with cardiovascular risk factors, carotid intima-media thickness (cIMT), presence of atherosclerotic plaques, plaque vulnerability, clinical symptoms, and ischemic stroke. Out of 148 articles initially identified, 49 met the inclusion criteria and were analyzed in depth. Among the different classes of ncRNAs, microRNAs (miRNAs) were the most frequently reported as dysregulated, followed by circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs). Notably, the majority of identified ncRNAs were implicated in key pathogenic mechanisms such as inflammatory signaling, vascular smooth muscle cell (VSMC) phenotypic modulation, and ABCA1-mediated cholesterol efflux. Collectively, the evidence underscores the association and possible involvement of ncRNAs in the initiation and progression of carotid atherosclerosis and its cerebrovascular complications. Their relative stability in biological fluids and cell-specific expression profiles highlight their strong potential as minimally invasive biomarkers and—possibly—novel therapeutic targets. Full article

Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID) arise from disruptions of molecular programmes that coordinate neurogenesis, synaptogenesis, and circuit maturation. While genomic studies have identified numerous susceptibility loci, genetic variation alone accounts for only part of disease heritability, underscoring the importance of post-transcriptional and epigenetic regulation. Among these regulatory layers, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), PIWI-interacting RNAs (piRNAs), and transfer RNA-derived small RNAs (tsRNAs), have emerged as central modulators of neural differentiation, synaptic plasticity, and intercellular signalling. Recent multi-omics and single-cell studies reveal that ncRNAs fine-tune chromatin accessibility, transcriptional output, and translation through tightly integrated regulatory networks. miRNAs shape neurogenic transitions and circuit refinement; lncRNAs and circRNAs couple chromatin architecture to activity-dependent transcription; and tsRNAs and piRNAs extend this regulation by linking translational control to epigenetic memory and environmental responsiveness. Spatial transcriptomics further maps ncRNA expression to vulnerable neuronal and glial subtypes across cortical and subcortical regions. Clinically, circulating ncRNAs, especially those packaged in extracellular vesicles, exhibit stable, disease-associated signatures, supporting their potential as minimally invasive biomarkers for early diagnosis and patient stratification. Parallel advances in RNA interference, antisense oligonucleotides, CRISPR-based editing, and vesicle-mediated delivery highlight emerging therapeutic opportunities. These developments position ncRNAs as both mechanistic determinants and translational targets in NDDs, offering a unifying framework that links genome regulation, environmental cues, and neural plasticity, and paving the way for next-generation RNA-guided diagnostics and therapeutics. Full article

Adenomyosis (AM) is a hormonally responsive uterine disorder defined by ectopic endometrial tissue within the myometrium, causing pain, abnormal bleeding, and subfertility. Non-coding RNAs (ncRNAs)—including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)—are post-transcriptional regulators implicated also in uterine remodeling. We systematically reviewed original studies evaluating ncRNAs in AM using human samples, in vitro and animal models, or bioinformatic approaches. Data sources included PubMed and Google Scholar (inception up to 10 August 2025). Forty-one studies were included and synthesized across mechanistic, diagnostic, and translational domains. miRNAs (n = 31) were the most studied subclass, followed by lncRNAs (n = 10) and circRNAs (n = 5). Recurrent miRNAs such as miR-10b and miR-30c-5p (downregulated, inhibitory) and miR-145 (upregulated, promotive) regulate epithelial invasion, epithelial–mesenchymal transition, and cytoskeletal remodeling via PI3K–AKT/MAPK and Talin1 signaling. The let-7a/LIN28B axis governed estrogen-sensitive proliferation in the junctional zone, while miR-21 exhibited compartment-specific roles in decidualization and ectopic cell survival. Extracellular-vesicle (EV)-bornemiRNAs (e.g., miR-92a-3p, miR-25-3p, miR-4669) contributed to immune polarization and show early diagnostic potential. lncRNAs and circRNAs acted via chromatin modifiers and ceRNA networks. Most findings remain at the discovery stage. Convergent dysregulation was observed in key signaling pathways, including JAK–STAT, Wnt/β-catenin, and Hippo–YAP. ncRNAs regulate critical axes of invasion, proliferation, immune modulation, and hormonal response in AM. Targets with preliminary causal support—miR-10b/ZEB1, let-7a/LIN28B, and miR-145/Talin1—warrant further validation. Circulating miRNAs—especially in EVs—offer promise for non-invasive diagnosis. Full article

Gastroesophageal cancers including esophageal and gastric cancer remain major causes of global cancer mortality, primarily due to late diagnosis and high recurrence rates after curative treatment. Current surveillance methods, such as endoscopy and imaging, are invasive, costly, and often inadequate for detection. Blood-based biomarkers (“liquid biopsies”) offer a minimally invasive alternative capable of real-time tumor monitoring. In this review, we summarize recent advances across all major classes of blood-derived biomarkers: circulating tumor DNA (ctDNA), methylated DNA, cell-free RNAs (microRNAs, lncRNAs, circRNAs), circulating proteins, autoantibodies, circulating tumor cells, extracellular vesicles, and metabolites. Reviewing the existing literature on gastroesophageal cancers, we highlight current evidence, validation phases, performance metrics, and limitations. Special attention is given to clinical trial evidence, including ctDNA monitoring studies, that demonstrated earlier recurrence detection compared to imaging. While blood-based biomarker analysis has not yet supplanted endoscopy as standard of care in gastroesophageal cancer surveillance, the convergence of multi-analyte assays, AI, and clinical validation trials positions liquid biopsy as a transformative tool in the surveillance of gastroesophageal cancers. Full article

Intracranial aneurysms (IAs) are potentially devastating cerebrovascular lesions, and predicting rupture risk remains a major clinical challenge. Conventional radiological and clinical scores offer only partial risk stratification, highlighting the need for complementary approaches. Liquid biopsy represents a promising non-invasive strategy to identify circulating biomarkers that reflect aneurysm biology and instability. We conducted a systematic review according to PRISMA 2020 guidelines, screening PubMed, Scopus, and Web of Science up to August 2025. Forty-eight eligible studies, encompassing 3515 IA patients, evaluated circulating RNA species, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in serum, plasma, blood, or cerebrospinal fluid. Multiple candidates emerged as consistently dysregulated: upregulation of miR-21, miR-126, and miR-200a-3p, and downregulation of miR-143 and let-7b-5p were recurrently observed across independent cohorts. LncRNAs, such as MALAT1 and MIAT, and circRNAs, including circ_0000690 and circ_0021001, demonstrated diagnostic and prognostic potential, with some correlating with rupture status and clinical severity indices. Despite encouraging findings, heterogeneity in study design, sample handling, and analytic methods limits reproducibility. Large-scale, multicenter validation studies are essential to translate these biomarkers into clinical practice. Full article

Postpartum metritis in dairy cows compromises reproductive performance and leads to substantial economic losses. This study investigated the molecular mechanisms underlying metritis by integrating high-throughput circulating microRNA (miRNA) profiling with systems-level bioinformatics. Previously, 30 differentially expressed miRNAs, 16 upregulated and 14 downregulated, were identified in metritis-affected cows compared to healthy controls. Building on these findings, this study predicted miRNA target genes and constructed regulatory networks involving miRNAs, mRNAs, circRNAs, lncRNAs, and snRNAs, alongside protein–protein interaction networks. Functional annotation and KEGG pathway analysis revealed that upregulated miRNAs influenced genes involved in immune activation, apoptosis, and metabolism, while downregulated miRNAs were associated with angiogenesis, immune suppression, and tissue repair. Hub genes such as AKT3, VEGFA, and HIF1A were central to immune and angiogenic signaling, whereas UBE3A and ZEB1 were linked to immune inhibition. Interferon-stimulated genes (e.g., ISG15, RSAD2, CXCL chemokines) were shown to regulate solute carriers, contributing to immune dysregulation. Key pathways included PI3K-Akt, NF-κB, JAK-STAT, insulin resistance, and T cell receptor signaling. Noncoding RNAs such as NEAT1, KCNQ1OT1, and XIST, along with miRNAs like bta-miR-15b and bta-miR-148a, emerged as pro-inflammatory regulators, while bta-miR-199a-3p appeared to exert immunosuppressive effects. These findings offer new insights into the complex regulatory networks driving metritis and suggest potential targets for improving fertility in dairy cows. Full article

Liquid biopsy has emerged as a valuable tool for the detection and monitoring of colorectal cancer (CRC), providing minimally invasive insights into tumor biology through circulating biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Additional biomarkers, including tumor-educated platelets (TEPs) and exosomal RNAs, offer further potential for early detection and prognostic role, although ongoing clinical validation is still needed. This review summarizes the current evidence on the diagnostic, prognostic, and predictive capabilities of liquid biopsy in both metastatic and non-metastatic CRC. In the non-metastatic setting, liquid biopsy is gaining traction in early detection through screening and in identifying minimal residual disease (MRD), potentially guiding adjuvant treatment and reducing overtreatment. In contrast, liquid biopsy is more established in metastatic CRC for monitoring treatment responses, clonal evolution, and mechanisms of resistance. The integration of ctDNA-guided treatment algorithms into clinical practice could optimize therapeutic strategies and minimize unnecessary interventions. Despite promising advances, challenges remain in assay standardization, early-stage sensitivity, and the integration of multi-omic data for comprehensive tumor profiling. Future efforts should focus on enhancing the sensitivity of liquid biopsy platforms, validating emerging biomarkers, and expanding multi-omic approaches to support more targeted and personalized treatment strategies across CRC stages. Full article

Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to cancer cell plasticity and facilitates epithelial-to-mesenchymal transition (EMT). Key histone modifiers, including KLF5, EZH2, and the demethylases KDM4/6, regulate osteoclastogenic signaling pathways and the transition between metastatic dormancy and reactivation. Simultaneously, SWI/SNF chromatin remodelers such as BRG1 and BRM reconfigure enhancer–promoter interactions that promote bone tropism. Non-coding RNAs, including miRNAs, lncRNAs, and circRNAs (e.g., miR-34a, NORAD, circIKBKB), circulate via exosomes to modulate the RANKL/OPG axis, thereby conditioning the bone microenvironment and fostering the formation of a pre-metastatic niche. These mechanistic insights have accelerated the development of epigenetic therapies. DNA methyltransferase inhibitors (e.g., decitabine, guadecitabine) have shown promise in attenuating osteoclast differentiation, while histone deacetylase inhibitors display context-dependent effects on tumor progression and bone remodeling. Inhibitors targeting EZH2, BET proteins, and KDM1A are now advancing through early-phase clinical trials, often in combination with bisphosphonates or immune checkpoint inhibitors. Moreover, novel approaches such as CRISPR/dCas9-based epigenome editing and RNA-targeted therapies offer locus-specific reprogramming potential. Together, these advances position epigenetic modulation as a promising axis in precision oncology aimed at interrupting the pathological crosstalk between tumor cells and the bone microenvironment. This review synthesizes current mechanistic understanding, evaluates the therapeutic landscape, and outlines the translational challenges ahead in leveraging epigenetic science to prevent and treat bone metastases. Full article

Analysis of tumoral RNA from bone marrow (BM) biopsy is essential for diagnosing childhood B-cell acute lymphoblastic leukemia (B-ALL), risk stratification, and monitoring, by detecting fusions and gene expression patterns. However, frequent BM biopsies are invasive and traumatic for patients. Small extracellular vesicles (sEVs) circulating in blood contain a variety of biomolecules, including RNA, that may contribute to cancer progression, offering a promising source of non-invasive biomarkers from liquid biopsies. While most EV studies have focused on small RNAs like microRNAs (miRNAs), the role of longer RNA species, including messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), remains underexplored despite their demonstrated potential for risk-based patient stratification when starting from BM biopsies. We used immuno-purification to isolate sEVs from peripheral blood at diagnosis in B-ALL patients and cell model-based conditioned culture medium (CCM) with ETV6::RUNX1 and TCF3::PBX1 fusions. Using whole-transcriptome sequencing targeting transcripts over 200 nt and a novel data analysis pipeline, we identified 102 RNA transcripts (67 mRNAs, 16 lncRNAs, 10 circRNAs, 4 pseudogenes, and 5 others) in patient-derived sEVs. These transcripts could serve as biomarkers for two distinct molecular subgroups of B-ALL, each with different risk profiles at diagnosis. This is the first study characterizing the long transcriptome in blood-derived sEVs for childhood B-ALL, highlighting the potential use of circulating RNAs for improved risk-based stratification. Full article

Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related mortality worldwide, with prognosis significantly deteriorating at advanced stages. While current diagnostic methods, such as colonoscopy and tissue biopsy, are widely employed in clinical practice, they are invasive, expensive, and limited in assessing tumor heterogeneity and monitoring disease processes, including therapy response. Therefore, early and accurate detection, coupled with minimal invasion and cost-effective strategies, are critical for improving patient outcomes. Liquid biopsy has emerged as a promising, minimally invasive alternative, enabling the detection of tumor-derived components. This approach is increasingly utilized in clinical settings. The current key liquid biopsy modalities in CRC include circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and RNA-based biomarkers such as long non-coding RNAs (lncRNAs), microRNAs(miRNAs), and circular RNAs (circRNAs), and tumor-educated platelets (TEPs). These methods provide valuable insights into genetic and epigenetic tumor alterations, and serve as indicators for early detection, treatment monitoring, and recurrence prediction. However, challenges such as assay standardization and variability in sensitivity persist. This review delves into the clinical applications of liquid biopsy in CRC management, highlighting the transformative roles of ctDNA, CTCs, and non-coding RNAs, TEPs in early detection, prognostic assessment, and personalized therapy. In addition, it addresses current limitations and explores potential advancements to facilitate their integration into routine clinical practice. Full article

The circular RNA circH19 has been implicated in the regulation of gene expression and various biological processes, including obesity. Objectives: This study aimed to elucidate the metabolic changes in plasma after circH19 knockdown in a diet-induced obese (DIO) mouse model. Methods: Plasma samples were collected following the intervention and subjected to non-targeted metabolomics analysis using liquid chromatography–mass spectrometry (LC-MS). Metabolic profiling was performed to identify and quantify metabolites, followed by multivariate statistical analysis to discern differential metabolic signatures. Results: A total of 1250 features were quantified, resulting in the upregulation of 564 metabolites and the downregulation of 686 metabolites in the circH19 knockdown group compared to the control mice. Metabolic pathway analysis revealed disruptions in lipid metabolism, amino acid turnover, and energy production pathways. Notably, the intervention led to a substantial decrease in circulating lipids and alterations in the plasma amino acid profile, indicative of an impact on protein catabolism and anabolic processes. The observed shifts in lipid and amino acid metabolism suggest potential therapeutic avenues for obesity and related metabolic disorders. Conclusions: The circH19 knockdown in DIO mice led to significant alterations in plasma metabolites, highlighting its potential role in the regulation of obesity and metabolic disorders. Full article

Preeclampsia, a serious complication of pregnancy, involves intricate molecular and cellular mechanisms. Fetal microchimerism, where fetal cells persist within maternal tissues and in circulation, acts as a mechanistic link between placental dysfunction and maternal complications in the two-stage model of preeclampsia. Hormones, complements, and cytokines play pivotal roles in the pathophysiology, influencing immune responses, arterial remodeling, and endothelial function. Also, soluble HLA-G, involved in maternal–fetal immune tolerance, is reduced in preeclampsia. Hypoxia-inducible factor 1-alpha (Hif-α) dysregulation leads to placental abnormalities and preeclampsia-like symptoms. Alterations in matrix metalloproteinases (MMPs), endothelins (ETs), chemokines, and cytokines contribute to defective trophoblast invasion, endothelial dysfunction, and inflammation. Preeclampsia’s genetic complexity includes circRNAs, miRNAs, and lncRNAs. CircRNA_06354 is linked to early-onset preeclampsia by influencing trophoblast invasion via the hsa-miR-92a-3p/VEGF-A pathway. The dysregulation of C19MC, especially miR-519d and miR-517-5p, affects trophoblast function. Additionally, lncRNAs like IGFBP1 and EGFR-AS1, along with protein-coding genes, impact trophoblast regulation and angiogenesis, influencing both preeclampsia and fetal growth. Besides aberrations in CD31+ cells, other potential biomarkers such as MMPs, soluble HLA-G, and hCG hold promise for predicting preeclampsia and its complications. Therapeutic interventions targeting factors such as peroxisome PPAR-γ and endothelin receptors show potential in mitigating preeclampsia-related complications. In conclusion, preeclampsia is a complex disorder with a multifactorial etiology and pathogenesis. Fetal microchimerism, hormones, complements, and cytokines contribute to placental and endothelial dysfunction with inflammation. Identifying novel biomarkers and therapeutic targets offers promise for early diagnosis and effective management, ultimately reducing maternal and fetal morbidity and mortality. However, further research is warranted to translate these findings into clinical practice and enhance outcomes for at-risk women. Full article

Breast cancer (BC) is currently the most common neoplasm, the second leading cause of cancer death in women worldwide, and is a major health problem. The discovery of new biomarkers is crucial to improve our knowledge of breast cancer and strengthen our clinical approaches to diagnosis, prognosis, and follow-up. In recent decades, there has been increasing interest in circulating RNA (circRNA) as modulators of gene expression involved in tumor development and progression. The study of circulating circRNAs (ccircRNAs) in plasma may provide new non-invasive diagnostic, prognostic, and predictive biomarkers for BC. This review describes the latest findings on BC-associated ccircRNAs in plasma and their clinical utility. Several ccircRNAs in plasma have shown great potential as BC biomarkers, especially from a diagnostic point of view. Mechanistically, most of the reported BC-associated ccircRNAs are involved in the regulation of cell survival, proliferation, and invasion, mainly via MAPK/AKT signaling pathways. However, the study of circRNAs is a relatively new area of research, and a larger number of studies will be crucial to confirm their potential as plasma biomarkers and to understand their involvement in BC. Full article

In recent years, EVs have emerged as promising vehicles for coding and non-coding RNAs (ncRNAs), which have demonstrated remarkable potential as biomarkers for various diseases, including chronic liver diseases (CLDs). EVs are small, membrane-bound particles released by cells, carrying an arsenal of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and other ncRNA species, such as piRNAs, circRNAs, and tsRNAs. These ncRNAs act as key regulators of gene expression, splicing, and translation, providing a comprehensive molecular snapshot of the cells of origin. The non-invasive nature of EV sampling, typically via blood or serum collection, makes them highly attractive candidates for clinical biomarker applications. Moreover, EV-encapsulated ncRNAs offer unique advantages over traditional cell-free ncRNAs due to their enhanced stability within the EVs, hence allowing for their detection in circulation for extended periods and enabling more sensitive and reliable biomarker measurements. Numerous studies have investigated the potential of EV-enclosed ncRNAs as biomarkers for CLD. MiRNAs, in particular, have gained significant attention due to their ability to rapidly respond to changes in cellular stress and inflammation, hallmarks of CLD pathogenesis. Elevated levels of specific miRNAs have been consistently associated with various CLD subtypes, including metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), and chronic hepatitis B and C. LncRNAs have also emerged as promising biomarkers for CLD. These transcripts are involved in a wide range of cellular processes, including liver regeneration, fibrosis, and cancer progression. Studies have shown that lncRNA expression profiles can distinguish between different CLD subtypes, providing valuable insights into disease progression and therapeutic response. Promising EV-enclosed ncRNA biomarkers for CLD included miR-122 (elevated levels of miR-122 are associated with MASLD progression and liver fibrosis), miR-21 (increased expression of miR-21 is linked to liver inflammation and fibrosis in CLD patients), miR-192 (elevated levels of miR-192 are associated with more advanced stages of CLD, including cirrhosis and HCC), LncRNA HOTAIR (increased HOTAIR expression is associated with MASLD progression and MASH development), and LncRNA H19 (dysregulation of H19 expression is linked to liver fibrosis and HCC progression). In the present review, we focus on the EV-enclosed ncRNAs as promising tools for the diagnosis and monitoring of CLD of various etiologies. Full article