Search Results (3,189)

Structural and functional disruptions of the epigenome are hallmarks of breast and ovarian carcinogenesis. This review dissects the reciprocal regulatory networks co-operated by DNA methyltransferases (DNMTs), ten-eleven translocation enzymes (TETs), and key non-coding RNAs (microRNAs and lncRNAs). We map the precise molecular mechanisms through which these epigenetic modulators alter chromatin accessibility, drive transcriptional reprogramming, and promote phenotypic plasticity in hormone-dependent malignancies. By systematically contrasting the distinct yet overlapping epigenetic profiles of breast and ovarian tumors, we elucidate how these aberrations dictate clinical outcomes. This comprehensive synthesis offers critical insights into the dual utility of these epigenetic elements as dual-purpose diagnostic biomarkers and druggable therapeutic targets, laying the groundwork for next-generation targeted epigenetical therapies. Full article

Malignant gliomas are highly aggressive primary brain tumors for which the therapeutic efficacy of cisplatin is frequently limited by intrinsic or acquired drug resistance. Despite advances in adjuvant therapies, overcoming chemoresistance remains a major challenge in the treatment of these malignancies. Emerging evidence indicates that long non-coding RNAs (lncRNAs), a class of non-protein-coding transcripts involved in gene regulation, play important roles in modulating treatment responses. Several lncRNAs, including differentiation antagonizing non-protein-coding RNA (DANCR), HOXD antisense growth-associated long non-coding RNA (HOXD-AS1), MEG3, MALAT1, and HOTAIR, have been implicated in pathways associated with glioma progression and therapeutic resistance. In particular, DANCR has been reported to promote cisplatin resistance in glioma cells through suppression of apoptosis and activation of pro-survival signaling pathways. This review summarizes current evidence regarding the roles of lncRNAs in cisplatin resistance, highlighting mechanisms such as regulation of drug transport, DNA damage repair, apoptosis, cancer stem-cell maintenance, and signaling pathways associated with treatment adaptation. We also discuss current limitations, challenges for clinical translation, and gaps in the existing evidence. A better understanding of lncRNA-mediated resistance mechanisms may facilitate the identification of novel therapeutic targets and inform future studies aimed at overcoming cisplatin resistance in malignant gliomas. Full article

Characterized by its highly aggressive behavior and propensity for metastasis, osteosarcoma remains a formidable clinical challenge with restricted treatment modalities. Cancer stem-like cells (CSCs) are widely recognized as central orchestrators of oncogenic progression and therapeutic intractability; however, the precise epigenetic regulations governing these processes are yet to be fully elucidated. Here, we investigated the role of the long non-coding RNA DANCR in regulating osteosarcoma stemness. DANCR expression was significantly upregulated in human osteosarcoma tissues and positively correlated with the stemness markers CD133, SOX2, and CD90. Functional assays demonstrated that DANCR overexpression enhanced stem-like properties, including an enriched CD133+/CD44+ cellular fraction and enhanced spheroid-forming capacity, concurrently accelerating in vitro cellular proliferation, migration, and invasive potential. In a xenograft mouse model, DANCR upregulation promoted in vivo tumor growth and lung metastasis. Mechanistically, dual-luciferase reporter assays and RNA immunoprecipitation (RIP) revealed that DANCR acts as a competing endogenous RNA (ceRNA) by sponging miR-145-5p, thereby facilitating the de-repression of CD133 and contributing to Akt/mTOR signaling activation. In addition, DANCR/miR-145-5p modulation was associated with changes in autophagy-associated markers. Collectively, these findings identify the DANCR/miR-145-5p/CD133 axis as a regulator of osteosarcoma stemness and progression, providing new insights into tumor biology and highlighting a potential molecular target for therapeutic investigation. Full article

Background/Objectives: Long non-coding RNAs (lncRNAs) are regulatory transcripts that contribute to diverse cellular processes and are increasingly recognized for their involvement in human diseases including cancer. In this context, long intergenic non-protein-coding RNA 1770 (LINC01770), also known as RRFERV, has been involved in nasopharyngeal cancer progression. However, its role in breast cancer (BC) remains unexplored. Here, we propose that LINC01770 plays a pivotal role in the development of aggressiveness traits such as invasion, migration, stemness, and tumorigenesis in BC cells. Methods: The LINC01770 overexpression was performed in BC cells using lentiviral transduction. Stemness and epithelial–mesenchymal transition markers, CD133⁺/44⁺ populations, cell migration, cell invasion, tumorigenesis in vitro, and chemoresistance were subsequently assessed via quantitative reverse transcription polymerase chain reaction (RT-qPCR), flow cytometry, Boyden chambers, soft agar, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays, respectively. LINC01770 expression in BC tissues and mechanistic analyses were performed in silico. Results: LINC01770 promotes cell migration and invasion accompanied by increased expression of EMT-associated genes. Moreover, elevated LINC01770 levels lead to an expansion of CD133⁺/CD44⁺ cell populations and upregulation of stemness-related genes as well as increase tumorigenic capacity in vitro. In contrast, no significant effects on drug resistance were observed. Finally, bioinformatic analyses suggest a putative LINC01770/miR-335-5p/OCT4 regulatory axis, consistent with the observed increase in OCT4 expression after LINC01770 overexpression. Conclusions: Our findings demonstrate that LINC01770 drives BC progression by promoting migration, invasion, and stemness features via the miR-335-5p/OCT4 axis. To our knowledge, this is the first study identifying LINC01770 as a potential therapeutic target in BC. Full article

Clinical genomics has traditionally focused on protein-coding variation, yet many pathogenic mechanisms arise through alterations in RNA processing, stability, localisation, translation, and surveillance. Prior reviews have addressed individual RNA layers, splicing, non-coding RNAs, RNA therapeutics, or RNA diagnostics in isolation. This review presents an integrated, mechanism-matched framework linking RNA-level disease mechanisms to diagnostic reasoning and therapeutic selection across all major RNA layers, offering a practical resource for clinical geneticists and translational researchers. I examine how splicing defects, pseudoexon inclusion, polyadenylation disruption, RNA editing loss, untranslated-region variants, premature termination codons, stop-loss variants, RNA-binding protein dysfunction, non-coding RNA dysregulation, altered codon usage, ribosome stalling, and surveillance pathway failure, including nonsense-mediated decay, nonstop decay, and no-go decay, each create distinct and mechanistically addressable disease states. A central argument of this review is that treatment selection must be mechanism-matched rather than gene- or variant-class-based: splice defects may require antisense oligonucleotide (ASO)-mediated correction or small-molecule splice modulation; toxic transcripts may require ASO- or siRNA-mediated silencing; haploinsufficiency may require mRNA replacement or transcript rescue; premature termination codons are candidates for readthrough only when transcript and protein context are favourable. I further argue that RNA sequencing, long-read transcriptomics, allele-specific expression analysis, and functional assays are essential for both diagnosis and therapeutic stratification. The framework described here moves clinical variant interpretation beyond descriptive classification toward mechanism-based, RNA-centric precision medicine. Full article

The study investigates the impact of molecular iodine (I₂) supplementation on the viability, invasiveness, and angiogenic potential of high-risk neuroblastoma (NB). In vitro assays were performed using NB cell lines SK-N-AS (non-MYCN-amplified) and SK-N-BE(2) (MYCN-amplified). The role of peroxisome proliferator-activated receptor gamma (PPARγ) was evaluated using the antagonist GW9662, gene expression (RT-qPCR), and protein levels (Western blot). In vivo, zebrafish xenografts were used to evaluate tumor size, angiogenesis, and caudal cell dissemination. I₂ supplementation significantly decreased cell viability in both cell lines, independent of PPARγ activation. In SK-N-BE(2), I₂ impaired cell migration, as measured by a wound-healing assay, in apparent independence of PPARγ activation. However, gene expression indicates that I₂ acts in complex ways, including direct antioxidant effects and PPARγ-mediated effects. The significant decrease in reactive oxygen species levels (DCFDA staining) and the silencing of the long noncoding RNA myocardial infarction-associated transcript (MIAT) by I₂ were directly associated with decreased MYCN and TrkB expression. In contrast, PPARγ activation was accompanied by overexpression of FasN and TrkA and a significant decrease in Aurka, a MYCN-stabilizing protein. In zebrafish, I₂-pretreated SK-N-BE(2) xenografts exhibited a clear reduction in angiogenesis (vascular density) and a decrease in invasive capacity. In conclusion, I₂ supplementation decreases cell viability and attenuates invasion and angiogenesis in NB cells, highlighting its potential as an adjuvant to conventional therapy for high-risk NB. Full article

Background: Safflower (Carthamus tinctorius L.) is a high-value economic crop with broad applications in agriculture, industry, and traditional medicine. Seed germination and seedling establishment are critical stages in the safflower life cycle, as they directly influence subsequent seedling establishment, survival, and plant growth. However, the transcriptomic dynamics and regulatory mechanisms underlying these processes remain largely unexplored, and the functional roles of long non-coding RNAs (lncRNAs) in this context are also poorly understood. Methods: In this study, transcriptome sequencing was performed across five developmental stages from seed germination to seedling establishment in safflower, followed by a comprehensive transcriptomic analysis and lncRNA identification. Results: Transcriptome sequencing identified a total of 3027 lncRNAs, including 940 natural antisense transcript (NAT)-pair-associated lncRNAs, which were classified into the divergent, convergent, and chimeric categories. Among these, 767 lncNATs were differentially expressed. Further analysis identified 542 NAT pairs in which both the protein-coding gene and its corresponding lncNAT exhibited a differential expression across the five developmental stages. A functional enrichment analysis of the predicted target genes of these lncRNAs suggested their involvement in photosynthesis and hormone-related responses. An enrichment analysis of differentially expressed genes (DEGs) across developmental stages further revealed the significant enrichment of photosynthesis and plant hormone signal transduction-related pathways, suggesting that these pathways are closely associated with safflower seed germination and seedling establishment. A further analysis of photosynthesis-related genes, particularly the expression patterns of LHC family members, suggested that Stage 3 may represent an important developmental transition associated with the optimization of the light-harvesting capacity during early seedling establishment, whereas plant-hormone-related genes are involved in regulating seed germination and subsequent leaf growth during seedling establishment. In addition, a weighted gene co-expression network analysis (WGCNA) identified candidate transcription factors associated with photomorphogenesis and plant hormone responses in safflower. Conclusions: This study advances our understanding of the regulatory mechanisms underlying safflower seed germination and subsequent growth and provides valuable molecular resources for future safflower breeding programs. Full article

Emerging evidence shows long non-coding RNAs (lncRNAs) as critical regulators of osteoarthritis (OA) progression, often acting in complex networks with microRNAs (miRNAs). In our study, we investigated the potential regulatory function of the lncRNA MEG3/miR-21-5p axis in the OA phenotype of chondrocytes. Differential gene expression analysis in damaged vs. intact cartilage was performed, re-analyzing existing public RNA-seq data. MiRTarBase, LncRNADisease, and Open Targets databases were utilized to identify miR-21-5p target genes and OA-associated lncRNAs and genes. Functional enrichment analysis and protein–protein interaction (PPI) network construction were performed using the DAVID and STRING databases, respectively. MEG3, miR-21-5p, SOX5, COL2A1 and ACAN mRNA expressions were assessed by qRT-PCR. The role of the MEG3/miR-21-5p axis in OA chondrocytes was examined using transfection experiments. Eighty-one lncRNAs displayed significant differences in expression between damaged and intact cartilage, including MEG3. Bioinformatic analysis indicated that MEG3 interacts with miR-21-5p, while SOX5 was identified to be a putative target of miR-21-5p. MEG3 and SOX5 expression levels were significantly downregulated in OA chondrocytes, whereas miR-21-5p expression was upregulated. Silencing of MEG3 resulted in increased miR-21-5p levels in chondrocytes. Conversely, inhibition of miR-21-5p led to increased SOX5 expression and anabolic markers COL2A1 and ACAN. Notably, MEG3 silencing significantly reduced SOX5 expression, an effect that was reversed upon miR-21-5p inhibition. Our findings highlight a potential regulatory role of the dysregulated MEG3/miR-21-5p axis in modulating the anabolic phenotype of chondrocytes through regulation of SOX5 expression. This novel lncRNA/miRNA/mRNA regulatory network may represent a candidate therapeutic axis for knee osteoarthritis. Full article

Background: Minimal change disease (MCD) is a leading cause of childhood nephrotic syndrome. Endoplasmic reticulum stress (ERS) and autophagy are implicated in its pathogenesis, but the precise mechanisms remain unclear. This study aimed to identify ERS and autophagy-related key genes (ERS-RGs and ARGs) in MCD using bioinformatic and experimental approaches. Methods: Transcriptomic data from GSE216841 and GSE246206 were analyzed. ERS-RGs and ARGs were obtained from prior literature. Candidate genes were selected by integrating weighted gene coexpression network analysis and differential expression analysis. Feature genes were identified via protein–protein interaction network analysis and machine learning (Least Absolute Shrinkage and Selection Operator and Boruta). Key genes were validated by expression analysis and receiver operating characteristic evaluation. A multilayer perceptron (MLP) model was constructed, and regulatory networks, immune infiltration, and chemical compound prediction were analyzed. The expression levels of the identified key genes were preliminarily assessed in peripheral blood samples using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results: LIG4 and ZRANB3 were identified as key genes, both significantly downregulated in the MCD group, and the gene-based MLP model effectively predicted MCD probability. Overall, 13 significantly different immune cell types (e.g., CD56⁺ natural killer and activated dendritic cells) were detected. Regulatory networks (transcription factor-messenger RNA (mRNA) and long non-coding RNA-microRNA-mRNA) and 8 common chemical compounds (e.g., bisphenol A, acetaminophen) targeting these genes were predicted. Notably, peripheral blood RT-qPCR analysis revealed significant LIG4 and ZRANB3 downregulation, suggesting a systemic expression signature. Conclusion: LIG4 and ZRANB3 are key genes associated with ERS and autophagy in MCD, providing insights for diagnosis and targeted therapy. Full article

Background: HCC remains one of the leading causes of cancer-related mortality worldwide, and the therapeutic efficacy of sorafenib is limited by the development of acquired resistance. Increasing evidence indicates that the tumor microenvironment, particularly HSCs, plays a pivotal role in modulating drug response; however, the underlying molecular mechanisms remain incompletely elucidated. Methods: Co-culture systems, mouse models, and biochemical assays were employed to evaluate the effects of HSCs on sorafenib sensitivity and ferroptosis in HCC cells. Transcriptomic analyses of data from The Cancer Genome Atlas were performed to identify key long non-coding RNAs (lncRNAs), followed by gain- and loss-of-function experiments to determine their biological roles. The underlying molecular mechanisms were further investigated through expression profiling, correlation analyses, and RNA stability assays. Results: HSCs markedly reduced the sensitivity of HCC cells to sorafenib by inhibiting ferroptosis, as evidenced by decreased levels of ferrous iron, reactive oxygen species, and lipid peroxidation, accompanied by increased glutathione content and activation of the NRF2 signaling pathway. LINC00152 was identified as a critical lncRNA that was upregulated in both HCC tissues and HCC cells co-cultured with HSCs, and its high expression was associated with poor prognosis. Functional studies demonstrated that LINC00152 promoted sorafenib resistance and suppressed ferroptosis both in vitro and in vivo. Mechanistically, LINC00152 enhanced HSPB1 expression by stabilizing its mRNA. Notably, HSPB1 knockdown reversed the effects of LINC00152, restoring ferroptosis and drug sensitivity to sorafenib. Conclusions: These findings reveal a novel HSCs–LINC00152–HSPB1 axis that promotes ferroptosis resistance and sorafenib tolerance in HCC. Targeting this pathway may represent a promising therapeutic strategy for overcoming drug resistance and improving clinical outcomes in patients with HCC. Full article

Alcohol-associated liver cirrhosis (ALC) lacks aetiology-specific molecular diagnostic biomarkers. This study aims to quantify the association between alcohol and cirrhosis risk, and to identify transcriptomic diagnostic biomarkers and candidate therapeutics. Methods: Survey-weighted logistic regression was applied to 17,007 adults from NHANES (2017–2023) to quantify alcohol-cirrhosis associations. ALC transcriptomic data from four GEO datasets were analysed using weighted gene co-expression network analysis (WGCNA) and three parallel machine learning algorithms (LASSO, Random Forest, SVM-RFE). External validation was performed in an independent cohort of 93 samples. Candidate therapeutics were identified via drug signature database querying and validated by molecular docking. Heavy drinking conferred a 5.14-fold increased cirrhosis risk (95% CI: 2.60–10.20, p < 0.001). Transcriptomic analysis revealed global downregulation of long non-coding RNAs (with 91.7% of dysregulated lncRNAs being suppressed). A five-gene diagnostic signature (IL1B, CCL3, LUM, SPP1, ITGA6), specifically developed to distinguish ALC from histologically normal liver tissue, achieved an area under the receiver operating characteristic curve (AUC) of 0.824 in an external validation cohort. Immune infiltration analysis uncovered global contraction of macrophage-associated transcriptomic signatures across M0, M1, and M2 subtypes, inversely correlated with fibrotic hub gene upregulation. Fluvastatin and honokiol were identified as candidate therapeutic agents, with strong binding affinities to IL1B and CCL3, respectively. This study confirms a dose-dependent alcohol-cirrhosis association and establishes a five-gene diagnostic signature (distinguishing ALC from normal liver tissue) alongside candidate therapeutics, warranting prospective clinical validation. The identified tissue-derived signature and therapeutic candidates provide a foundation for future ALC-specific diagnostic and therapeutic strategies; their translation into a non-invasive (e.g., blood-based) assay will require dedicated validation in circulating samples. Full article

Yaks have long inhabited the Qinghai-Tibetan Plateau. This region features low-oxygen, frigid temperatures and pronounced seasonal variation in nutrient availability. They have evolved adaptive phenotypes centered on energy metabolism reprogramming, tissue structure remodeling, and stress homeostasis maintenance. In recent years, non-coding RNAs (ncRNAs) have been confirmed as an important component of the yak’s post-transcriptional regulatory network. They play a key bridging role between environmental stress perception and phenotypic output through mechanisms such as influencing RNA splicing, stability, translation activity, and constructing competitive endogenous RNA (ceRNA) networks. This article systematically reviews the biogenesis pathways and core regulatory patterns of circular RNAs (circRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). It focuses on summarizing the expression profile characteristics and dynamic spatiotemporal changes of these three types of ncRNAs in physiological contexts such as muscle and fat deposition, mammary gland lactation, testicular development, and hypoxia response in the heart, lungs, and vascular system of yaks. Current research evidence indicates that the regulatory network of yaks ncRNAs shows significant convergence on multiple key signaling pathways, mainly concentrating on lipid metabolism (PPAR/AMPK), nutrition and growth signals (PI3K-Akt/MAPK/mTOR), extracellular matrix remodeling (ECM-receptor interaction, Wnt/TGF-β), and cell stress fate determination (apoptosis, oxidative stress/ferroptosis) modules. Among them, some core circRNA and lncRNA-miRNA-mRNA regulatory axes have been functionally validated in vitro. Despite the phased progress, current research on ncRNA in yaks still faces bottlenecks: the multi-omics molecular atlases (encompassing genomics, transcriptomics, proteomics, and metabolomics) of key high-altitude adaptive organs remain incomplete, analysis processes lack sufficient standardization, and most studies stay at the association network level with limited causal mechanism validation. To address these limitations, future research should focus on building a standardized evidence chain, integrating multi-omics and single-cell/spatial transcriptome technologies, and conducting mechanism verification for traits in independent populations, thereby providing a solid theoretical basis for understanding the extreme environmental adaptation mechanisms of yaks and molecular breeding improvement. Full article

Camel milk is increasingly recognized as a premium functional food, attributed to its rich nutraceutical compounds. Recent research has concentrated on the nanoscale extracellular vesicles derived from camel milk (CM-EVs), which exhibit distinctive properties. This review examines the methodologies for isolating and characterizing CM-EVs, alongside their potential health benefits in functional foods and nutraceuticals. CM-EVs have the capacity to safeguard functional proteins, noncoding RNAs, and bioactive lipids from degradation within the gastrointestinal tract, rendering them particularly suitable for incorporation into infant formulas, adult dietary supplements, and nutraceuticals targeting chronic inflammatory and metabolic disorders. Preclinical models indicate that CM-EVs can mitigate oxidative stress, enhance intestinal barrier integrity, and modulate gut microbiota, thereby contributing to the reduction in colonic injury and inflammation. Nonetheless, the majority of these findings are derived from laboratory and animal studies, highlighting a substantial deficiency in human clinical trials. Critical research gaps remain, necessitating further investigation into the elucidation of molecular mechanisms, assessment of long-term safety, evaluation of bioavailability, and compatibility with dairy processing techniques. This review underscores the significance of CM-EVs as bioactive food components and delineates research priorities, such as standardizing isolation methods, investigating food matrix integration, and providing translational evidence for their application in nutrition and preventive medicine. Full article

Background/Objectives: Inflammatory and oxidative-stress-related processes contribute to post-myocardial infarction (MI) remodeling and may influence long-term cardiovascular outcomes. Recent findings have highlighted the potential role of non-coding RNAs in regulating these processes. LncRNA MALAT1 acts as a ceRNA that “sponges” miR-146a, reducing its ability to repress downstream targets such as COX-2. The aim of this study was to assess MALAT1 and miR-146a expression in PBMCs and plasma COX-2 in controls and patients six months post-MI. In addition, we investigated whether MALAT1 rs3200401 and miR-146a rs2910164 variants were associated with MI susceptibility, MALAT1 and miR-146a expression, plasma COX-2 levels, and left ventricle (LV) echocardiographic parameters. Methods: The study included 534 patients and 381 controls for genetic analyses, while expression analyses were performed in a subset of 89 patients and 39 controls. TaqMan™ assays were used for genotyping and for quantification of MALAT1 and miR-146a expression. Plasma COX-2 levels were measured using ELISA. Results: Compared to controls, patients had higher MALAT1 expression, whereas lower miR-146a expression was observed only in unadjusted analyses. Plasma COX-2 levels were higher in patients with advanced heart failure (NYHA III–IV) compared with NYHA I-II. The rs3200401 TT genotype was more frequent in patients, whereas rs2910164 genotype distributions were similar between groups. The rs3200401-rs2910164 TG allele combination was associated with increased MI risk. Conclusions: MALAT1 may serve as a potential long-term biomarker of post-MI molecular alterations, whereas the role of miR-146a requires further investigation in larger cohorts. The rs3200401 variant may represent a genetic marker associated with MI susceptibility and adverse LV remodeling. Further studies are needed for confirmation. Full article

The multifaceted oncogenic role of teratocarcinoma-derived growth factor 1 (TDGF1) in colon cancer remains incompletely understood. Through integrative bioinformatic and functional analyses, we identified a novel competing endogenous RNA (ceRNA) axis wherein the long non-coding RNA OLMALINC directly sponges hsa-miR-3614-5p, leading to the derepression of TDGF1. This OLMALINC/miR-3614-5p/TDGF1 axis promoted colon cancer cell proliferation, migration, invasion, and anti-apoptosis in vitro, whereas TDGF1 knockdown significantly suppressed tumor growth in vivo. Mechanistically, TDGF1 co-activated oncogenic signaling via the Thr88-dependent Nodal/Smad2 cascade and the Glypican-1-mediated MAPK/AKT pathway. Beyond cell-autonomous effects, transcriptomic and single-cell analyses revealed that elevated TDGF1 correlates with an immunosuppressive microenvironment, characterized by reduced immune infiltration and altered LGALS9-CD44 malignant-T cell communication. Clinically, high TDGF1 expression in a tissue microarray cohort was significantly associated with advanced T stage, reduced expression of specific mismatch repair proteins (MLH1/PMS2), and poor overall survival. Collectively, this study delineates the OLMALINC/miR-3614-5p/TDGF1 regulatory circuit and establishes TDGF1 as a multifaceted driver of tumor progression, highlighting its potential as a prognostic biomarker and therapeutic target in colon cancer. Full article