Search Results (1,393)

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and are usually driven by activating mutations in KIT or PDGFRA. Although these alterations define the core molecular biology of GISTs and guide targeted therapy, they do not fully explain the variability observed in tumor behavior, recurrence risk, or response to tyrosine kinase inhibitors. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been increasingly studied as regulators of gene expression in GISTs. Recent evidence suggests that these molecules may influence KIT-centered signaling, autophagy, apoptosis, invasion, angiogenesis, and drug resistance. However, the strength of evidence differs considerably across individual ncRNAs, ranging from bioinformatic associations to functional validation in cell lines and in vivo models. This review summarizes current knowledge on ncRNA-mediated regulation in GIST biology, with emphasis on tumor progression, therapeutic resistance, and possible clinical relevance. Rather than treating ncRNAs as isolated biomarkers, they function as part of broader regulatory networks that interact with oncogenic signaling and epigenetic mechanisms. Although several ncRNAs appear promising as prognostic or predictive candidates, further validation in independent clinical cohorts is required before their integration into routine risk stratification or treatment decision-making. Full article

Background: Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disorder (prevalence 1:500), a major substrate of sudden cardiac death (SCD) in adolescents and young adults, and is modulated by regulatory mechanisms including non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long non-coding RNAS (lncRNAs) and circular RNAs (circRNAs), which act as epigenetic modulators and potential biomarkers. Methods: The study involves a PRISMA-based systematic review of 989 records from PubMed, Scopus, Embase, Web of Science and Cochrane, including 96 studies evaluating ncRNAs as diagnostic, prognostic, genotype-specific or mechanistic markers in clinically/genetically confirmed HCM. Human biomarker studies (circulating/tissue ncRNAs) were analyzed separately from experimental models (human myocardium, animal models, iPSC-derived cardiomyocytes, cardiac organoids). Results: Key findings include upregulated miR-29a, miR-21 and miR-133a in HCM plasma/tissue (correlating with hypertrophy/fibrosis), miR-499a-5p as an MYH7-specific marker, and miR-208b-3p/miR-155 associated with MYBPC3-related HCM. Pro-hypertrophic lncRNAs (e.g., NEAT1, UCA1), fibrotic lncRNAs (e.g., MIAT) and protective/mitochondrial circRNAs (e.g., circZFPM2) contribute to ceRNA networks linking hypertrophy, fibrosis, mitochondrial dysfunction and arrhythmic remodeling. Multi-ncRNA panels have shown discriminatory performance between HCM and selected phenocopies, while some signatures have been associated with atrial fibrillation and composite cardiac outcomes; however, these findings remain heterogeneous and require independent validation. Conclusions: NcRNAs are biologically relevant regulators of HCM and represent promising candidates for mechanistic investigation, biomarker development and, potentially, therapeutic targeting. Current clinical evidence remains insufficient to support their incorporation into established SCD risk prediction models or their use as standalone diagnostic tools, particularly given the heterogeneity of cohorts, sample sources and analytical approaches. Their potential forensic relevance is also exploratory: ncRNA profiling may provide an additional molecular layer for the characterization of cardiomyopathic substrates in unexplained SCD, but its specificity, post-mortem stability and incremental value over conventional autopsy, histopathology and molecular autopsy remain unestablished. Dedicated longitudinal clinical and forensic studies are required before ncRNAs can be considered for routine clinical or post-mortem application. Full article

RNA therapeutics have evolved from passive genetic intermediaries into highly programmable platforms, fundamentally transforming the landscape of precision medicine. This comprehensive review examines the molecular architecture and mechanisms of established platforms in the clinical setting, including mRNA, antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs) and aptamers, alongside next-generation platforms, such as CRISPR-guided systems and circular RNAs (circRNAs). Moreover, we discuss strategies to overcome systemic delivery bottlenecks and evaluate advanced non-viral systems, emphasizing lipid nanoparticles (LNPs), polymers and tissue-specific ligand conjugates that facilitate precise intracellular targeting. Furthermore, we explore the clinical expansion of these platforms across infectious diseases, rare genetic disorders, oncology and cardiovascular conditions. Finally, we highlight how the integration of artificial intelligence (AI) and machine learning (ML) redefines the limits of individualized, programmable RNA therapies by accelerating sequence optimization and nanoparticle formulation. Full article

CircRNAs are covalently closed ncRNAs originating through back splicing; their expression is finely regulated, displaying specific patterns across different cell types, tissues, and developmental stages. While the molecular functions of circRNAs are not completely elucidated, their regulatory involvement in physiological processes is well established, alongside their dysregulation in several human disorders. These features, together with their higher stability compared to other ncRNAs, make this class of molecules promising theragnostic agents, particularly in biomarker discovery. Accordingly, it is crucial to develop and standardize experimental strategies that improve circRNA analysis, ensuring accurate and effective isolation of these molecules. In biomarker discovery, selecting the appropriate biological matrix is critical; whole blood is often preferred for its accessibility and minimally invasive collection. Because circRNAs are present in human peripheral blood and show promise as disease theragnostic biomarkers, we established a preliminary workflow tailored to isolate and analyze circRNAs from whole blood. The promising effectiveness and robustness of this workflow were demonstrated by qPCR analysis, suggesting highly reproducible detection and reliability in isolating and analyzing circRNAs. This, together with their stability and specific expression profiles, supports the utility of circRNAs in biomarker discovery and advanced circRNA research and contributes to accelerating their future integration into theragnostic applications in clinical settings. Full article

Skeletal muscle is a continuously load-bearing tissue whose growth, repair, and age-related decline are governed by mechanical signals; failure of this mechano-regulation underlies disuse atrophy and sarcopenia. Piezo1, a mechanically activated cation channel, has emerged as a tractable transducer of these signals in muscle, contributing to satellite-cell quiescence and senescence, regenerative division, myoblast fusion, and the response to loading and unloading. In parallel, the myogenic noncoding RNA program is among the best defined in any lineage, with myomiRs miR-1/133/206, the long noncoding RNA LINC-MD1, and the circular RNA circ-ZNF609 being established regulators of the proliferation-to-differentiation transition. These layers are linked because Piezo1-evoked calcium influx feeds the RhoA/ROCK-actin-MRTFA-SRF and YAP/TAZ axis that drives myogenic transcription, yet no direct coupling between Piezo1 and noncoding RNAs has been demonstrated in skeletal myocytes. Drawing on validated precedents from vascular, cardiac, and tendon tissues, this review consolidates the two pillars, frames their convergence as a testable question, distinguishes validated relationships from hypotheses, and proposes three falsifiable predictions using an unbiased candidate selection strategy. The contribution of this review is this testable framework rather than any specific candidate list. Mechanically tunable noncoding RNAs may thus represent an underexplored node for counteracting disuse atrophy and sarcopenia. Full article

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of clinically aggressive mature T-cell and natural killer (NK)-cell neoplasms that account for approximately 10–15% of all non-Hodgkin lymphomas in Western countries . The most common subtypes include extranodal NK/T-cell lymphoma (ENKTL), nodal T-follicular helper cell lymphomas, peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), anaplastic large cell lymphoma (ALK-positive and ALK-negative), and T-cell lymphoblastic lymphoma. Non-coding RNAs (ncRNAs) constitute the majority of the human transcriptome and play critical roles in regulating gene expression, cellular proliferation, differentiation, migration, and apoptosis. Among these, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) have emerged as key regulators of lymphomagenesis and disease progression in PTCLs. These molecules modulate diverse oncogenic pathways through chromatin remodeling, transcriptional regulation, competing endogenous RNA activity, and interactions with RNA-binding proteins, thereby influencing proliferation, immune evasion, treatment resistance, and clinical outcomes. Representative examples include the lncRNA TCLlnc1, which promotes PTCL progression through activation of transforming growth factor-β (TGF-β) signaling, and the circRNAs circKIF4A, circADARB1, and circ-LAMP1, which regulate miRNA-dependent signaling networks involving PDK1/BCL11A, STAT3, and DDR2, respectively. In this review, we summarize the current understanding of the biological and clinical roles of lncRNAs and circRNAs in PTCL and related T-cell and NK-cell neoplasms and highlight their potential as diagnostic and prognostic biomarkers as well as therapeutic targets. We also discuss recent advances and future directions for integrating ncRNA-based approaches into precision medicine for T-cell lymphoma. Full article

Vairimorpha ceranae, an obligate intracellular parasitic fungus, infects the midgut of worker Apis cerana cerana, disrupts nutritional metabolism and immune homeostasis of hosts, and poses severe threats to honeybee health and the sustainable development of apiculture. To date, the expression dynamics of circular RNAs (circRNAs) during pathogen infection and their regulatory functions as competing endogenous RNAs (ceRNAs) remain poorly characterized. In this study, circRNA sequencing was performed on purified V. ceranae spores (VcCK), as well as the midguts of A. cerana cerana worker bees at 7 days post-infection (VcT1) and 10 days post-infection (VcT2). A total of 8,986,470 and 315 circRNAs were identified from the three groups, with their lengths predominantly ranging from 200 to 600 nt. Differential expression analysis screened 575 and 594 differentially expressed circRNAs (DEcircRNAs) from the VcCK vs. VcT1 and VcCK vs. VcT2 comparison groups, respectively. The host genes generating these DEcircRNAs were annotated to 316 and 310 GO terms, alongside 167 KEGG pathways. CeRNA network analysis revealed that DEcircRNAs including novel_circ_006653 target multiple miRNAs, and their downstream target mRNAs are significantly enriched in energy metabolism pathways such as carbon metabolism and glycolysis/gluconeogenesis. RT-qPCR validation exhibited high consistency with transcriptome sequencing data. Further analyses demonstrated that V. ceranae infection drastically remodels the circRNA expression landscape: the total number of circRNAs was sharply reduced, and the dominant circRNA subtype shifted from antisense circRNAs to single-exon circRNAs. Several DEcircRNAs (novel_circ_006653, novel_circ_004839, novel_circ_005596, etc.) may participate in pathogen infection progression via the ceRNA regulatory axis by modulating host energy metabolism, immune responses and cellular biological processes. This study provides novel insights into the molecular interaction mechanisms between microsporidian parasites and their honeybee hosts, and identifies potential molecular targets for the prevention and control of microsporidiosis. Full article

Fowl adenovirus serotype 4 (FAdV-4) is the major pathogen responsible for avian hepatitis–hydropericardium syndrome (HHS), which poses a severe threat to the global poultry industry. This study aimed to systematically explore virus–host interactions and elucidate the transcriptomic alterations and underlying molecular mechanisms in LMH cells following FAdV-4 infection. LMH cells were infected with FAdV-4 at a multiplicity of infection (MOI) of 1 for 24 h, and whole-transcriptome sequencing was subsequently performed. Differential expression analysis was conducted between the FAdV-4-infected group and the uninfected Mock group, followed by functional interaction prediction. Quantitative polymerase chain reaction (qPCR) was used to verify the expression profiles of differentially expressed genes (DEGs). The results identified a total of 8292 differentially expressed messenger RNAs (dif-mRNAs), 80 differentially expressed microRNAs (dif-miRNAs), 3263 differentially expressed long non-coding RNAs (dif-lncRNAs), and 52 differentially expressed circular RNAs (dif-circRNAs) in the infected group compared with the Mock group. The identified DEGs were further validated and subjected to Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Additionally, protein–protein interaction (PPI) analysis and regulatory network analyses of lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA were performed. This study provides novel insights and research perspectives into the potential mechanisms underlying FAdV-4–host interactions and further deepens the current understanding of the pathogenesis of FAdV-4 infection. Full article

IBs are mineralized spicules originating from osteoblasts differentiated from tenocytes that can reduce the commercial value of fish and pose potential health risks to consumers if accidentally ingested. Runx2b exhibited higher expression in osteoblasts associated with IBs. Knockout of the runx2b gene significantly reduced osteoblast numbers and completely inhibited IB formation, confirming its essential role in osteogenic differentiation. However, how non-coding RNAs regulate this process during IB formation remains poorly understood. In this study, whole-transcriptome sequencing was performed to identify ncRNAs and mRNAs in dorsal and tail muscle tissues from six-month-old M. amblycephala with IBs (WT group, n = 3) and without IBs (Mut group, n = 3). A total of 1762 and 1992 differentially expressed (DE) transcripts were identified in dorsal and tail muscle, respectively. Specifically, in dorsal muscle, 408 DE-circular RNAs (circRNAs), 425 DE-long non-coding RNAs (lncRNAs), 171 DE-microRNAs (miRNAs), and 758 DE-messenger RNAs (mRNAs) were detected; in tail muscle, 337 DE-circRNAs, 414 DE-lncRNAs, 222 DE-miRNAs, and 1019 DE-mRNAs were identified. Gene Set Enrichment Analysis (GSEA) revealed that, in the Mut group, key osteogenic signaling pathways, specifically Wnt, MAPK, and TGF-β, were significantly enriched among downregulated genes. Several key IB formation-responsive ceRNAs were identified based on correlation analysis, and the expression and function of the critical regulatory axis, lnc007185570.1–pal-miR-3120-3p–ppp3cb, were experimentally validated. Functional assays subsequently demonstrated that this axis modulates osteoblast differentiation via the Wnt signaling pathway. These findings offer new insights into the molecular mechanisms governing osteoblast differentiation during IB formation from the perspective of ceRNA regulatory networks. Full article

Cancer stem cells (CSCs) drive therapeutic resistance, metastasis, and tumor recurrence through reversible transitions among stem-like, differentiated, epithelial, and mesenchymal states, which are sustained by interconnected epigenetic mechanisms. To our knowledge, this is the first review to integrate curcumin-mediated regulation of DNA methylation, chromatin remodeling, and non-coding RNAs within a single CSC plasticity framework and to propose the concept of an “epigenetic collapse of CSC plasticity” as a mechanistic explanation for how curcumin may weaken stemness, state switching, and adaptive treatment resistance. Evidence was critically evaluated through structured searches of PubMed/MEDLINE, Scopus, Web of Science Core Collection, Google Scholar, and citation tracking, while direct curcumin–epigenetic evidence was distinguished from independent CSC evidence and inferential mechanistic links. Curcumin has been reported to modulate DNMT1 and locus-specific DNA methylation; regulate HDACs, p300/CBP, EZH2, H3K27me3, and BMI1; and alter selected microRNA, long non-coding RNA, and circular RNA pathways, with comparatively stronger evidence involving the miR-34 family, miR-200c, miR-21, H19, and circHN1. However, current evidence is constrained by the predominance of bulk cancer-cell models, heterogeneous formulations and exposure conditions, and the scarcity of epigenetic rescue experiments combined with rigorous functional CSC assays. By unifying previously fragmented epigenetic evidence, this review advances a new evidence-weighted model in which curcumin may suppress CSC persistence not through a single molecular target, but by destabilizing the multilayer epigenetic circuitry that enables plasticity. Curcumin should therefore be regarded as a context-dependent, multilayer epigenetic modulator rather than an established CSC-eradicating therapy, and its translational relevance requires validation in prospectively defined CSC models with pharmacologically justified delivery and exposure conditions. Full article

Lung cancer ranks first in both incidence and mortality among all malignancies, and tumor microenvironment (TME)-induced CD8⁺ T cell exhaustion is a critical factor driving immune evasion and compromising the efficacy of immunotherapy. MicroRNAs (miRNAs), as key post-transcriptional regulators, shuttle between lung cancer cells and CD8⁺ T cells via extracellular vesicles (EVs), serving as critical communication hubs that reshape the TME. This review systematically synthesizes recent literature to summarize the regulatory patterns of miRNAs on functions of lung cancer cells and CD8⁺ T cells, and dissect the molecular mechanisms underlying miRNA-mediated bidirectional crosstalk between these two cell types. This review focuses on the dual-pronged immune evasion strategy employed by lung cancer cells to counteract CD8⁺ T cells. On the one hand, lung cancer cells aberrantly express endogenous miRNAs, such as miR-20a, miR-149-5p, and miR-326, to remodel their surface ligands and establish immune camouflage. On the other hand, they actively secrete EVs enriched in specific miRNAs, including miR-7108-3p, miR-651-5p, and miR-24-3p, which directly suppress CD8⁺ T cell function. Furthermore, lung cancer cells secrete additional miRNAs, notably miR-6794-5p, miR-708-5p, and miR-1234-3p, to reprogram other TME components, namely tumor-associated macrophages (TAMs), natural killer (NK) cells, and myeloid-derived suppressor cells (MDSCs). These reprogrammed cells, in turn, indirectly attenuate CD8⁺ T cells through a relay-like mechanism via immunosuppressive cytokines or surface checkpoint molecules produced by these cells. In addition, competing endogenous RNA (ceRNA) networks formed by long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in lung cancer cells regulate miRNA activity at multiple levels, further impairing the immune effector functions of CD8⁺ T cells. Conversely, activated CD8⁺ T cells also secrete miRNA-containing EVs, which deliver these miRNAs to tumor cells, thereby inhibiting tumor progression. Elucidation of this miRNA-based bidirectional communication network will not only advance our understanding of immune evasion mechanisms in lung cancer but also provide novel insights into cell-free immunotherapeutic approaches based on CD8⁺ T cell-derived vesicles. Full article

Background: Circular RNAs (circRNAs) constitute an emerging research field, as these RNA molecules play a crucial role in cellular functions and the progression of various human pathologies. Little is known about alternative circularization leading to the formation of distinct circRNAs from the same primary transcript, the role of circRNAs with slightly different back-splice junctions (BSJs) resulting in very similar circRNA sequences—called circRNA isoforms—and the extent to which the same primary transcripts produce alternative circRNAs. In this study, we discovered alternative circRNAs produced by two apoptosis-related genes, BAX and BCL2L12, expressed in established human cell lines originating from myelodysplastic syndrome (MDS) and different types of acute myeloid leukemia (AML). Methods: After total RNA extraction from one MDS cell line and five AML cell lines, first-strand cDNA synthesis, and multiple nested PCRs with distinct sets of divergent primers (10 and 16 primer pairs for BAX and BCL2L12 circRNAs, respectively) annealing in each exon of BAX and BCL2L12 genes, amplicon libraries were prepared and sequenced by both nanopore sequencing and NGS. Detailed bioinformatic analysis was then performed, based on existing bioinformatic tools and our own algorithms. Results: Our approach led to the identification of 72 BAX circRNAs and 52 BCL2L12 circRNAs with distinct expression patterns in MDS and AML cell lines. Most of these circRNAs—either merely exonic or exonic–intronic—were detected for the very first time. Furthermore, several BAX circRNA isoforms were detected in a unique cell line. Moreover, the back-splice sites joined together to form the BSJ of each circRNA were non-canonical, in many cases. The identified circRNAs are predicted to sponge distinct sets of miRNAs, some of which are known to regulate the activity of pivotal pathways. Conclusions: Overall, our findings support the notion that alternative splicing and back-splicing lead to the production of tens of distinct circRNAs from the same human gene. Full article

Respiratory diseases impose a substantial global burden; however, early diagnosis, disease-activity monitoring, and the clinical translation of nucleic acid therapeutics are constrained by the lack of robust biomarkers and efficient delivery systems. This narrative review focuses on four classes of RNA—messenger RNA (mRNA), circular RNA (circRNA), small interfering RNA (siRNA), and microRNA (miRNA)—using exosomes as a representative subtype of extracellular vesicles (EVs) to discuss EV biogenesis, transport, uptake, and engineered cargo loading. We summarize the diagnostic and therapeutic applications of EV-associated nucleic acids in chronic or non-severe respiratory diseases, including asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and cystic fibrosis, as well as in severe acute conditions such as acute respiratory distress syndrome and severe pneumonia. Biofluid-derived EV-associated RNAs can reflect inflammation, immune dysregulation, epithelial injury, infection, and fibrosis, supporting their potential use in disease classification, monitoring, and prognostic assessment. Natural EVs may modulate inflammation and tissue repair through their endogenous cargo, while engineered EVs can deliver therapeutic nucleic acids to exert anti-inflammatory, anti-infective, antifibrotic, and barrier-restorative effects. However, clinical translation is limited by non-standardized isolation and characterization methods, product heterogeneity, variable cargo loading, and insufficient stability and quality-control frameworks. Continued advances in EV isolation, characterization, nucleic acid loading, potency assessment, and manufacturing control are required to realize the diagnostic and therapeutic potential of EV-associated nucleic acids in respiratory diseases. Full article

We explored the potential functions of differentially expressed miRNAs, mRNAs, lncRNAs, and circRNAs identified in the ovaries of gilts with normal estrus (NE) and follicular cyst-associated anestrus (AE), as well as their putative competing endogenous RNA (ceRNA) regulatory networks. Ovarian morphology was assessed via ultrasonography, and serum concentrations of Follicle-stimulating hormone (FSH), (Estradiol) E2, and Progesterone(P4) were measured. Ovarian tissues were harvested after slaughter for whole-transcriptome sequencing. Bioinformatic tools were used to screen differentially expressed RNAs(DERNAs) between NE and AE gilts. We further predicted target interactions among these transcripts, conducted functional enrichment analysis on target genes, and constructed candidate ceRNA regulatory networks potentially associated with gilt estrus. Phenotypic verification confirmed that ovarian ultrasonographic characteristics, histological morphology, and serum reproductive hormone levels were consistent with the physiological status of NE and AE gilts. Under the screening thresholds of p < 0.05 and |log₂FC| ≥ 1, we identified 22 lncRNAs that may interact with 21 mRNAs via 50 miRNAs, alongside 39 circRNAs predicted to regulate 26 mRNAs through 72 miRNAs. Functional enrichment analysis indicated that target genes of these differentially expressed transcripts were predominantly enriched in the lysosome pathway, PPAR signaling pathway, chemokine signaling pathway, cholesterol metabolism and NOD-like receptor signaling pathway. Hub molecules including FGF1, GHR, TLR2, ssc-miR-370, and miR-21-5p were shared in lncRNA/circRNA-miRNA-mRNA regulatory networks; these molecules have been reported to participate in progesterone synthesis, estrus modulation, and endocrine homeostasis. Of particular interest, two non-coding RNAs, MSTRG.1285.1 and novel_circ_056113, were predicted to act as candidate ceRNAs that may sponge ssc-miR-370 and miR-21-5p, which could in turn modulate the expression of estrus-associated mRNAs including FGF1, GHR, and TLR2. The expression trends of MSTRG.1285.1, novel_circ_056113, miR-370, miR-21-5p, GHR, TLR2, and FGF1 were validated by qRT-PCR, and the quantification results agreed with transcriptome sequencing data. Collectively, this study constructed a predicted ceRNA regulatory network of ovarian transcripts comparing NE and AE gilts and uncovered multiple RNA molecules potentially involved in estrus regulation. These findings offer preliminary theoretical clues for exploring the onset of puberty in gilts. Full article

Adipose tissue development significantly influences meat quality and economic traits in beef cattle. In this study, we identified a novel circular RNA derived from two exons (exons 3 and exons 9) of the NID2 gene, designated as circNID2, which exhibits high structural stability and marked upregulation during bovine adipocyte differentiation. Functional assays demonstrated that circNID2 suppresses the proliferation and apoptosis of bovine preadipocytes while robustly promoting adipogenic differentiation and lipid accumulation. Although containing several putative open reading frames, circNID2 lacks protein-coding potential. Mechanistically, circNID2 functions as a competing endogenous RNA by sponging miR-339a, thereby relieving the post-transcriptional repression of its downstream target, Neuronatin (NNAT). Functional rescue experiments further validated that circNID2 partially neutralizes the regulatory effects of miR-339a on preadipocyte proliferation, apoptosis, and differentiation. Collectively, these findings demonstrate that circNID2 regulates bovine preadipocyte function through the newly established circNID2/miR-339a/NNAT axis. This study provides novel insights into the post-transcriptional mechanisms governing mammalian adipogenesis and highlights circNID2 as a potential molecular target for improving fat deposition traits in cattle. Full article