Search Results (2,079)

The identification of microRNAs (miRNAs) has resulted in significant advancements in research, particularly regarding their utilization as diagnostic and therapeutic targets. This has generated enthusiasm for exploring the potential of non-coding RNAs (ncRNAs) in treating cancer and other diseases, with miRNAs and long non-coding RNAs (lncRNAs) showing particular promise. Over the past twelve years, there has been significant research into RNA-based treatments. Antisense oligonucleotides and small interfering RNAs are the most commonly used. Certain products have received Federal and Drug Administration approval. Notably, the findings from clinical trials have been inconsistent, with certain investigations indicating notable effectiveness and others reporting only minimal efficacy or safety concerns. Consequently, clinical trials are currently underway to evaluate the efficacy of novel treatment options, including antimiRNAs, in addressing these challenges. There is an increasing interest in the use of long non-coding RNA (lncRNA)-based therapies. The potential for drugs developed using this technology is significant. Significant advancements in preclinical and clinical trials have emerged, indicating promising potential for future developments. MiRNAs are playing an increasingly important role in the diagnosis and prediction of acute coronary syndrome manifestations. Its utilization, whether as a comprehensive approach or in conjunction with existing biomarkers, may be implemented in the foreseeable future, especially in instances of uncertainty regarding diagnosis. The primary objective of this review is to deliver a thorough and detailed assessment of recent progress in the field of microRNA detection and characterization. A key focus of this assessment will be on their clinical translation. Secondly, an exploration of the prevailing knowledge in the field of RNA therapies as potential targets for diagnosis and treatment in the cardiovascular system will be conducted. The most recent challenges and perspectives on the road to clinical application are presented herein. The aim of the present seminar is to furnish a thorough report on the recent advancements in the detection and characterization of miRNAs and lncRNAs, with specific emphasis on their clinical translation. In summary, the paper herein presents an exploration of the most recent challenges and perspectives on the road to clinical application. Full article

Vairimorpha ceranae is a fungal pathogen that infects the honeybee midgut and poses a serious threat to colony health. However, the role of long noncoding RNAs (lncRNAs) of V. ceranae in its infection of the host remains poorly understood. Using lncRNA-seq data from the midguts of Apis mellifera workers at 7 and 10 days post-inoculation with V. ceranae (NcT1L and NcT2L groups), along with controls inoculated with spores (NcCKL group), we performed transcriptome-wide identification and structural characterization of lncRNAs. We identified lncRNAs in V. ceranae and analyzed the regulatory network of the differentially expressed lncRNAs (DElncRNAs). A total of 27 V. ceranae lncRNAs were identified in the midguts. The 19, 21, and 4 DElncRNAs were identified in the NcCKL vs. NcT1L, NcCKL vs. NcT2L, and NcT1L vs. NcT2L comparison groups. These DElncRNAs were predicted to regulate 26, 27, and 2 upstream/downstream genes. Furthermore, 15, 23, and 4 DElncRNAs were found to target 195, 211, and 94 miRNAs, which in turn targeted 204, 216, and 73 mRNAs into the respective comparisons. The ceRNA network prediction revealed that DElncRNAs, miRNAs and mRNAs form a complex regulatory network. This study presents the expression profile of lncRNAs during V. ceranae infection and highlights their potential regulatory functions in pathogenesis. Our findings provide new molecular insights into host–pathogen interactions at the RNA level and establish a foundation for developing targeted strategies to control nosemosis. Full article

Piscirickettsia salmonis is one of the most significant pathogens affecting salmon farming. Besides liver, head kidney and spleen, skeletal muscle has shown transcriptional immune responses to these bacteria, but the contribution of non-coding RNAs remains poorly understood. This study investigates the role of long non-coding RNAs (lncRNAs) in the immune response of rainbow trout skeletal muscle and primary myotube cultures infected with P. salmonis. Using RNA-seq data from both in vivo and in vitro muscle under control and infected conditions, the analysis identified 4263 candidate lncRNAs through a stringent bioinformatics pipeline. These lncRNAs were mostly classified as exonic and intergenic, showing distinct genomic distributions and structural differences depending on the source. Expression analyses revealed that cell type had a stronger effect on lncRNA profiles than infection status. From 764 differentially expressed lncRNAs, 191 were uniquely associated with infected and 180 with control conditions, mainly unannotated. Functional predictions based on co-expression and proximity to coding genes suggest that lncRNAs are primarily involved in downregulation of structural-cellular maintenance under control conditions, whereas during infection, they are related to immunity, signaling, and apoptosis. Overall, the findings indicate that lncRNAs exhibit origin-specific regulatory roles and are modulated by P. salmonis infection, highlighting their potential importance in fish immune responses. Full article

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

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

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: 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

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

In hepatocellular carcinoma (HepG2), aberrant histone modifications are closely linked to long non-coding RNA (lncRNA) expression. However, existing computational models lack physical interpretability at specific promoter coordinates. To address this, we developed a position-specific statistical scoring model based on adjacent and next-adjacent nucleotide frequencies. We trained two independent, position-specific matrices representing increased and decreased modification states across 600 bp promoter windows centered on the true signal summits. Finally, ten-fold cross-validation revealed that significant energy differences between sequences with increased and decreased histone signals enable excellent classification performance. These results indicted a strong correlation between the total energy of local DNA structures and histone modification signal. Full article

Background/Objectives: Long non-coding RNAs (lncRNAs) have been identified as potential biomarkers for cancer diagnosis and prognosis. In the present study, we proposed the analysis of four lncRNAs as a diagnostic support candidate for the follow-up of leukemia patients. The aim of this study was to characterize the expression of BALR6, LINC-PINT, MEG3, and ZEB1-AS1 in patients with B-cell acute lymphoblastic leukemia (B-ALL) at diagnosis and at the end of remission induction therapy. Methods: B-ALL diagnosis and MRD assessment were performed by flow cytometry, while lncRNA expression levels were quantified using TaqMan probe-based assays. Results: Fifteen pediatric patients with B-ALL were followed longitudinally. MRD evaluation identified seven refractory and eight remitted patients. Significant expression changes were observed for MEG3 in remitted patients and for BALR6 and LINC-PINT in refractory patients. No statistically significant differences were detected for ZEB1-AS1. Conclusions: Changes in MEG3, LINC-PINT, and BALR6 lncRNA expression are associated with treatment response and MRD status in pediatric B-ALL, supporting their potential role as complementary biomarkers to conventional MRD monitoring. Full article

Background/Objectives: Cervical cancer is mainly driven by persistent infection with high-risk human papillomaviruses (HPV), particularly HPV16 and HPV18. Despite advances in cytology, HPV-DNA testing and vaccination, challenges remain in the triage of HPV-positive individuals, prognostic stratification and prediction of treatment response. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs, together with host genetic factors influencing ncRNA expression and emerging lncRNA-encoded peptides, are increasingly recognized as regulators of HPV-associated carcinogenesis. This review summarizes their biological and potential clinical relevance. Methods: A structured literature search was conducted in PubMed and Scopus. Eligible studies included experimental, clinical, observational, genomic and translational investigations on ncRNA dysregulation, circulating or exosomal ncRNAs, treatment-response signatures, host genetic variation and lncRNA-encoded peptides in HPV-associated cervical precancer and cancer. Results: HPV oncoproteins can reshape host ncRNA networks through transcriptional and epigenetic mechanisms. Several miRNAs, lncRNAs and circRNAs are involved in cell-cycle control, apoptosis, senescence, epithelial–mesenchymal transition, immune regulation, DNA repair and treatment resistance. Circulating, exosomal and urinary ncRNA signatures have shown diagnostic or prognostic potential in exploratory cohorts. Specific lncRNAs, including ENSG00000267838/lnc-LENG9-5 and lncRNA-EME1, have been associated with chemoradiotherapy response and radioresistance. The lncRNA-encoded peptide TUBORF represents a novel preclinical therapeutic candidate, while genetic variation may further modulate lncRNA function in HPV-related cervical cancer. Conclusions: ncRNAs are promising candidates for risk stratification, non-invasive diagnosis, treatment-response prediction and therapeutic development in HPV-associated cervical disease. However, evidence remains exploratory, requiring prospective multicentre validation and standardized workflows before clinical implementation. Full article