Search Results (172)

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

Herpesviruses are DNA viruses that evade the immune response and persist as lifelong infections. Human gamma-herpesviruses Epstein–Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV) are oncogenic; they can lead to cancer. Oncogenic viruses are responsible for 10–15% of human cancer development, which can have poor prognoses. Non-coding RNAs (ncRNAs) are RNAs that regulate gene expression without encoding proteins, and are being studied for their roles in viral immune evasion, infection, and oncogenesis. ncRNAs are classified by their size, and include long non-coding RNAs, microRNAs, and circular RNAs. EBV and KSHV manipulate host ncRNAs, and encode their own ncRNAs, regulating host processes and immune responses. Viral ncRNAs regulate host functions by post-transcriptionally modifying host RNAs, and by serving as mimics of other host RNAs, promoting immune evasion. ncRNAs in gamma-herpesvirus infection are also important for tumorigenesis, as dampening immune responses via ncRNAs can upregulate pro-tumorigenic pathways. Emerging topics such as RNA modifications, target-directed miRNA degradation, competing endogenous RNA networks, and lncRNA/circRNA–miRNA interactions provide new insights into ncRNA functions. This review compares ncRNAs and the mechanisms of viral immune evasion in EBV and KSHV, while also expanding on recent developments in the roles of ncRNAs in immune evasion, viral infection, and oncogenesis. Full article

Lead (Pb) exposure poses a significant public health concern due to its neurotoxic effects. While mitochondrial dysfunction is implicated in lead neurotoxicity, the precise molecular mechanisms, particularly the role of non-coding RNA-mediated competing endogenous RNA networks, remain underexplored. SH-SY5Y neuroblastoma cells were treated with 10 μM lead acetate. Cell viability was assessed by Cell Counting Kit-8 (CCK-8). Mitochondrial ultrastructure and quantity were analyzed via transmission electron microscopy (TEM). Key mitochondrial dynamics proteins were examined by Western blot. Comprehensive transcriptome sequencing, including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs) and mRNAs, was performed followed by functional enrichment and ceRNA network construction. Selected RNAs and hub genes were validated using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Lead exposure significantly reduced SH-SY5Y cell viability and induced mitochondrial damage (decreased quantity, swelling, fragmentation). Western blot confirmed an imbalance in mitochondrial dynamics, as indicated by decreased mitofusin 2 (MFN2), increased total and phosphorylated dynamin-related protein 1 (DRP1). Transcriptomic analysis revealed widespread differential expression of lncRNAs, circRNAs, miRNAs, and mRNAs. Enrichment analysis highlighted mitochondrial function and oxidative stress pathways. A ceRNA network identified five key hub genes: SLC7A11, FOS, HMOX1, HGF, and NR4A1. All validated RNA and hub gene expression patterns were consistent with sequencing results. Our study demonstrates that lead exposure significantly impairs mitochondrial quantity and morphology in SH-SY5Y cells, likely via disrupted mitochondrial dynamics. We reveal the potential regulatory mechanisms of lead-induced neurotoxicity involving ceRNA networks, identifying hub genes crucial for cellular stress response. This research provides a foundational framework for developing therapeutic strategies against lead-induced neurotoxicity. Full article

Nucleobase and nucleoside analogs are critical components of antimetabolite chemotherapy treatments used to disrupt DNA replication and induce apoptosis in rapidly proliferating cancer cells. However, the development of resistance to these agents remains a major clinical challenge. This review explores the epigenetic mechanisms that contribute to acquired chemoresistance, focusing on DNA methylation, histone modifications, and non-coding RNAs (ncRNAs). These epigenetic alterations regulate key processes such as DNA repair, drug metabolism, cell transport, and autophagy, enabling cancer cells to survive and resist therapeutic pressure. We highlight how dysregulation of DNA methyltransferases (DNMTs) and histone acetyltransferases (HATs) modulates expression of transporters (e.g., hENT1, ABCB1), DNA repair enzymes (e.g., Polβ, BRCA1/2), and autophagy-related genes (e.g., CSNK2A1, BNIP3). Furthermore, emerging roles for long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in regulating nucleoside export and DNA damage response pathways underscore their relevance as therapeutic targets. The interplay of these epigenetic modifications drives resistance to agents such as gemcitabine and 5-fluorouracil across multiple tumor types. We also discuss recent progress in therapeutic interventions, including DNMT and HDAC inhibitors, RNA-based therapeutics, and CRISPR-based epigenome editing. Full article

Extracellular vesicles (EVs) are released by nearly all types of cells, and they communicate between cells by transporting bioactive molecules, including proteins, DNA, RNA, and lipids. In recent years, RNA carried by EVs, particularly the long-chain non-coding RNA (lncRNA) and circular RNA (circRNA) subtypes, has garnered interest with respect to their role in controlling tumor progression. Among them, there are increasing reports that mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) maintain a recently discovered function as transporters of lncRNAs and circRNAs. However, detailed molecular functions of lncRNAs and circRNAs contained in MSC-EVs are not presently summarized, and the efficacy of MSC-EVs as molecular carriers requires further elucidation. This review summarizes the biological characteristics of EVs and the common mechanisms of lncRNAs and circRNAs contained within them. The “double-edged sword” effect and related molecular mechanism of EV-derived lncRNAs (EV-lncRNAs) and circRNAs (EV-circRNAs) between differing tumor types and MSCs are highlighted. The potential of MSC-EVs in the field of tumor diagnosis and treatment is discussed to suggest new directions for the strategy of engineering MSC-EVs as anti-tumor drug carriers. Full article

T-cadherin (CDH13) is an atypical, glycosyl-phosphatidylinositol-anchored cadherin with functions ranging from axon guidance and vascular patterning to adipokine signaling and cell-fate specification. Originally identified as a homophilic cue for migrating neural crest cells, projecting axons, and growing blood vessels, it later emerged as a dual metabolic receptor for cardioprotective high-molecular-weight adiponectin and atherogenic low-density lipoproteins. We recently showed that mesenchymal stem/stromal cells lacking T-cadherin are predisposed to adipogenesis, underscoring its role in lineage choice. Emerging evidence indicates that CDH13 expression and function are fine-tuned by non-coding RNAs (ncRNAs). MiR-199b-5p, miR-377-3p, miR-23a/27a/24-2, and the miR-142 family directly bind CDH13 3′-UTR or its epigenetic regulators, affecting transcription or accelerating decay. Long non-coding RNAs (lncRNAs), including antisense transcripts CDH13-AS1/AS2, brain-restricted FEDORA, and context-dependent LINC00707 and UPAT, either sponge these miRNAs or recruit DNMT/TET enzymes to the CDH13 promoter. Circular RNAs (circRNAs), i.e.circCDH13 and circ_0000119, can add a third level of complexity by sequestering miRNA repressors or boosting DNMT1. Collectively, this ncRNA circuitry regulates T-cadherin across cardiovascular, metabolic, oncogenic, and neurodegenerative conditions. This review integrates both experimentally validated data and in silico predictions to map the ncRNA-CDH13 crosstalk between health and disease, opening new avenues for biomarker discovery and RNA-based therapeutics. Full article

In recent years, it has become clear that non-coding RNAs play an important role in regulating the development of various organs and pathological conditions, including cerebral ischemia and reperfusion. Non-coding RNAs are mainly represented by long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs). Most of the human genome is transcribed into such RNAs. Excessive activation of autophagy during cerebral ischemia and reperfusion results in autophagic neuronal death in addition to apoptotic death. This review shows that regulation occurs via the lncRNA (or circRNA)/miRNA/target protein signaling axes. A knockdown or a decrease in lncRNA level can lead to a significant increase in miRNA levels, followed by a decrease in the levels of messenger RNA (mRNA) of autophagy-related protein (ATG) and ATG protein itself. This leads to inhibition of autophagy and alleviation of brain ischemia–reperfusion injury. Changes in miRNA and mRNA levels of the target protein occur due to the presence of complementary nucleotide sequences with lncRNA and miRNA, respectively. If the target protein is not an ATG protein, neuroprotection during cerebral ischemia and reperfusion can result from both inhibition and activation of autophagy. The further study of the regulatory role of non-coding RNAs is important as it may help to counteract the effects of excessive autophagy activation and other adverse effects of ischemia–reperfusion injury Full article

Cholangiocarcinoma (CCA) is an aggressive tumor that originates from the epithelial cells of the bile duct and has the ability to metastasize to the liver or lymph nodes at an early stage. CCA metastasis represents a complex, multi-stage cascade process. Among these stages, the acquisition of invasiveness by CCA cells is a critical prerequisite for metastatic progression. Elucidating the molecular mechanisms driving CCA cell invasiveness is critical for advancing our knowledge in this field. Emerging evidence highlights the critical role of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). These molecules orchestrate key processes such as the epithelial–mesenchymal transition (EMT), as well as the migration and invasion of CCA cells. Collectively, these processes ultimately drive tumor progression. This review comprehensively synthesizes the expression, biogenesis, interactions, signaling pathways, and functional mechanisms of ncRNAs in the invasiveness of CCA. Furthermore, the review discusses potential clinical applications of ncRNAs, including their roles as diagnostic tools, therapeutic targets, and prognostic markers. These investigations offer novel insights and evidence for identifying early metastasis in CCA, developing specific therapeutic strategies, and enhancing drug resistance. Full article

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, leading to muscle weakness, paralysis, and eventually death. The pathogenesis of ALS is influenced by genetic factors, environmental factors, and age-related dysfunctions. These factors, taken together, are responsible for sporadic cases of ALS, which account for approximately 85–90% of ALS cases, while familial ALS accounts for the remaining 10–15% of cases, usually with dominant traits. Despite advances in understanding and studying the disease, the cause of the onset of ALS remains unknown. Emerging evidence suggests that non-coding RNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play crucial roles in the pathogenesis of the disease. An abnormal expression of these molecules is implicated in various ALS-related processes, including motor neuron survival, protein aggregation, and inflammation. Here, we describe the dysregulation of non-coding RNAs in the pathogenic mechanism of ALS, highlighting the potential roles of miRNAs, lncRNAs, and circRNAs as biomarkers or therapeutic targets to examine the progression of the disease. Full article

Background: Endometrial receptivity is crucial for successful embryo implantation in assisted reproductive technologies (ARTs). MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) have emerged as important post-transcriptional regulators of endometrial function, although their diagnostic and molecular functions are poorly understood. Methods: A systematic review was conducted following PRISMA 2020 principles and registered in PROSPERO (CRD420251001811). We looked at 28 peer-reviewed publications published between 2010 and 2025 that used endometrial tissue, blood, uterine fluid, saliva, and embryo culture medium to study miRNAs and other non-coding RNAs in endometrial receptivity, recurrent implantation failure (RIF), and infertility. Results: MiRNAs like miR-145, miR-30d, miR-223-3p, and miR-125b influence implantation-related pathways such as HOXA10, LIF-STAT3, PI3K-Akt, and Wnt/β-catenin. Dysregulated expression profiles were linked to inadequate decidualization, immunological imbalance, and poor angiogenesis. CeRNA networks that include lncRNAs (e.g., H19 and NEAT1) and circRNAs (e.g., circ_0038383) further regulate miRNA activity. Non-invasive biomarkers derived from plasma, uterine fluid, and embryo media showed high prediction accuracy for implantation outcomes. Conclusions: MiRNA signatures offer a functional and diagnostic blueprint for endometrial receptivity. This systematic review provides a timely and thorough synthesis of the existing literature, with the goal of bridging the gap between molecular discoveries and therapeutic applications. By emphasizing both the mechanistic importance and diagnostic value of certain miRNA signatures, it paves the way for future precision-based techniques in embryo transfer and endometrial assessment in ART. Full article

Adipocyte differentiation is a complex process in which pluripotent mesenchymal stem cells (MSCs) differentiate and develop into mature fat cells, also known as adipocytes. This process is controlled by various transcription factors, hormones, and signaling molecules that regulate the development of these cells. Recently, an increasing number of non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), have been established to be involved in the regulation of many biological processes, including adipocyte differentiation, development, metabolism, and energy homeostasis of white and brown adipose tissue. Several in vitro and in vivo studies reported the significant role of ncRNAs in either promoting or inhibiting adipocyte differentiation into white or brown fat cells by targeting specific transcription factors and regulating the expression of key adipogenic genes. Identifying the function of ncRNAs and their subsequent targets contributes to our understanding of how these molecules can be used as potential biomarkers and tools for therapies against obesity, diabetes, and other diseases related to obesity. This could also contribute to advancements in tissue-engineering based treatments. In this review, we intended to present an up-to-date comprehensive literature overview of the role of ncRNAs, including miRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), focusing particularly on miRNAs, in regulating the differentiation and development of cells into white and brown adipose tissue. In addition, we further discuss the potential use of these molecules as biomarkers for the development of novel therapeutic strategies for future personalized treatment options for patients. 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

Fat deposition represents a crucial feature in the expenditure of physical energy and affects the meat quality of farm animals. It is regulated by multiple genes and regulators. Of them, non-coding RNAs (ncRNAs) play a critical role in modulating the fat deposition process. As well as being an important protein source, farm animals can be used as medical models, so many researchers worldwide have explored their mechanism of fat deposition. This article summarizes the transcription factors, regulatory genes, and signaling pathways involved in the molecular regulation process of fat deposition; outlines the progress of researching the roles of microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) in fat deposition in common farm animals including pigs, cattle, sheep, ducks, and chickens; and identifies scientific problems in the field that must be further investigated. It has been demonstrated that ncRNAs play a critical role in regulating the fat deposition process and have great potential in improving meat quality traits. Full article

Sweetpotato is the seventh largest crop worldwide, and soil salinization is a major environmental stress limiting its yield. Recent studies have shown that noncoding RNAs (ncRNAs) play important regulatory roles in plant responses to abiotic stress. However, ncRNAs in sweetpotato remain largely unexplored. This study analyzed the characteristics of salt-responsive ncRNAs in sweetpotato adventitious roots under salt stress via whole-transcriptome RNA sequencing. The results revealed that 3175 messenger RNAs (mRNAs), 458 microRNAs (miRNAs), 544 long-chain ncRNAs (lncRNAs), and 23 circular RNAs (circRNAs) were differentially expressed. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that most differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) were enriched primarily in phenylpropanoid biosynthesis, starch and sucrose metabolism, the Mitogen-Activated Protein Kinase (MAPK) signaling pathway, plant hormone signal transduction, the mRNA surveillance pathway, and ATP-binding cassette (ABC) transporters. Gene Ontology (GO) enrichment analysis revealed that the majority of DEmRNAs, their target DEmiRNAs, and differentially expressed lncRNAs (DElncRNAs) were associated with the cell wall, oxidation–reduction, the plasma membrane, protein phosphorylation, metabolic processes, transcription factor activity, and the regulation of transcription. Additionally, based on the competitive endogenous RNA (ceRNA) hypothesis, we predicted interactions among different RNAs and constructed a salt-responsive ceRNA network comprising 22 DEmiRNAs, 42 DEmRNAs, 27 DElncRNAs, and 10 differentially expressed circRNAs (DEcircRNAs). Some miRNAs, such as miR408, miR169, miR160, miR5139, miR5368, and miR6179, were central to the network, suggesting their crucial roles in the sweetpotato salt response. Our findings provide a foundation for further research into the potential functions of ncRNAs and offer new targets for salt stress resistance improvement through the manipulation of ncRNAs. Full article