Search Results (172)

Background: Zika virus (ZIKV), a mosquito-borne flavivirus, is associated with congenital malformations and neuroinflammatory disorders, highlighting the need to identify host factors that shape infection outcomes. Macrophages, key targets and reservoirs of ZIKV, orchestrate both antiviral and inflammatory responses. Methods: Vitamin D (VitD) has emerged as a potent immunomodulator that enhances macrophage antimicrobial activity and regulates inflammation. To investigate how VitD shapes macrophage responses to ZIKV, we reanalyzed publicly available RNA-seq and miRNA-seq datasets from monocyte-derived macrophages (MDMs) of four donors, differentiated with or without VitD and subsequently infected with ZIKV. Results: Differential expression analysis identified long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs integrated into competing endogenous RNA (ceRNA) networks. In VitD-conditioned and ZIKV-infected MDMs, 65 lncRNAs and 23 miRNAs were significantly modulated. Notably, lncRNAs such as HSD11B1-AS1, Lnc-FOSL2, SPIRE-AS1, and PCAT7 were predicted to regulate immune and metabolic genes, including G0S2, FOSL2, PRELID3A, and FBP1. Among the miRNAs, let-7a and miR-494 were downregulated, while miR-146a, miR-708, and miR-378 were upregulated, all of which have been previously implicated in antiviral immunity. Functional enrichment analysis revealed pathways linked to metabolism, stress responses, and cell migration. ceRNA network analysis suggested that SOX2-OT and SLC9A3-AS1 may act as molecular sponges, modulating regulatory axes relevant to immune control and viral response. Conclusions: Despite limitations in sample size and experimental validation, this study provides an exploratory map of ncRNA–mRNA networks shaped by VitD during ZIKV infection, highlighting candidate molecules and pathways for further studies on host–virus interactions and VitD-mediated immune regulation. Full article

Background/Objectives: Circular RNAs (circRNAs) are emerging players in human diseases, with functions as part of competing endogenous networks. Given the importance of messenger RNA (mRNA) regulation in human diseases and the potential of circRNAs in this regulation, we studied the circRNA–mRNA couple in blood within a cohort of 712 patients suspected of having hereditary colorectal cancer (CRC) and 249 matched controls. Methods: The circRNA–mRNA couple was studied by SEALigHTS (Splice and Expression Analyses by exon Ligation and High-Throughput Sequencing) with a panel of 23 genes involved in CRC predisposition, comprising 788 probes designed at exon ends, enabling the exploration of all exon–exon junctions. Following reverse transcription and probe hybridization on cDNA, nearby probes were ligated, and the number of ligations was quantified using unique molecular identifiers and sequencing. Results: We identified 220 circular junctions, including 47 novel ones. The circRNA/mRNA ratio was 2.42-fold higher in patients compared to controls (p < 10⁻¹⁶), irrespective of age at cancer onset. This increase was mainly driven by POLD1 (fold change 3.84) and a single circPOLD1(3,2) with oncogenic potential Conclusions: This study supports the existence of a physiological balance between circRNA and mRNA that can be disrupted under pathological conditions. It rules out a competitive mechanism between circular and linear transcripts in CRC predisposition and raises questions about the role of specific circRNAs in the development of CRC, either as a cause or a consequence. Full article

Rising global temperatures lead to a continuous increase in the frequency and intensity of extreme weather events, such as droughts and floods, posing serious threats to terrestrial homeotherms. However, adaptive changes in respiratory metabolism and molecular mechanisms in lung tissues of small mammals under extreme water shortage conditions remain unclear. This study hypothesized that small desert mammals can adapt to extreme water shortage environments by regulating the plasticity of lung tissue gene expression and respiratory metabolism. Using 29 wild-caught Siberian jerboas (Orientallactaga sibirica) as subjects, we implemented a 12-day complete water deprivation protocol to simulate extreme aridity. Body weight, food intake, and daily energy expenditure (DEE) were monitored throughout the experiment. Whole-transcriptome sequencing of lung tissues was performed to profile mRNA, circRNA, and miRNA expression, with competitive endogenous RNA (ceRNA) network analysis to explore molecular mechanisms underlying lung adaptation to water deprivation. Over the 12-day water deprivation (WS) period, Orientallactaga sibirica (O. sibirica) exhibited a 30.3% reduction in body mass and a 68.1% decrease in food intake relative to the baseline level. DEE during the peak activity period at the end of the experiment was 12.6% lower in the WS group compared to the control group. In lung tissue, structural integrity-related genes (Mybl2, Ccnb1) were downregulated. A key finding was that circ_0015576 exhibits a significant positive correlation with the potassium channel gene Kcnk15 and a robust negative correlation with miR-503-5p—suggesting that circ_0015576 functions as a competing endogenous RNA (ceRNA) to sequester miR-503-5p and thereby derepress Kcnk15 expression. Core regulatory genes (ApoA4, Dusp15 etc.) were also coordinately downregulated. Collectively, these results indicate that O. sibirica reduces overall energy expenditure, which may be associated with lung gene expression plasticity, such as those related with lung cell proliferation, pulmonary function, and gas exchange efficiency. This metabolic downregulation facilitates energy conservation under severe water scarcity. Full article

Background/Objectives: Ovarian cancer (OC) remains one of the most lethal gynecological malignancies, mainly because it is frequently diagnosed at advanced stages due to nonspecific symptoms and the lack of effective screening strategies. Long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression, and accumulating evidence implicates them in OC initiation, progression, and treatment response. This review aims to comprehensively summarize the molecular mechanisms of lncRNAs in OC, examine their clinical potential as biomarkers, and discuss emerging technologies that are about to advance lncRNA research and therapeutics in OC. Methods: A comprehensive review of published studies investigating lncRNA expression, function, and clinical relevance in OC was conducted. Mechanistic insights were integrated across multiple regulatory levels, including epigenetic, transcriptional, post-transcriptional, and post-translational control. Advances in transcriptomic technologies and RNA-targeting techniques were also examined. Results: LncRNAs influence OC through diverse mechanisms, including chromatin remodeling, transcriptional regulation, RNA splicing, mRNA stability, protein modulation, competing endogenous RNA networks, and nuclear organization. Their dysregulation is linked to tumor progression, metastasis, chemoresistance, and poor patient outcomes. Numerous lncRNAs exhibit diagnostic and prognostic value, underscoring their clinical potential. Advances in long-read sequencing have improved lncRNA annotation and isoform resolution, while CRISPR-Cas13 offers a potential approach for selective RNA-targeted therapy. Conclusions: LncRNAs are critical molecules in OC development and progression, holding potential in advancing OC diagnosis, prognosis, and treatment. Continued integration of functional studies, advanced sequencing technologies, and RNA-targeting approaches can facilitate the clinical translation of lncRNAs for early OC diagnosis and management. Full article

Abiotic stress of cold is one of the limitation factors that hinder the production of alfalfa (Medicago sativa). Although there are a large number of studies suggesting that non-coding RNAs (ncRNAs) play an important role in plant response to abiotic stress, the mechanism by which ncRNAs and competing endogenous RNAs (ceRNAs) influence the low-temperature tolerance of alfalfa remains understudied. In this study, we integrated whole-transcriptome RNA-seq and genome-wide association studies (GWASs) to identify cold stress-related metabolic pathways and candidate genes, differentially expressed (DE) mRNAs, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Degradome sequencing was used to verify the ceRNA network under cold stress. A total of 46,936 DEmRNAs were identified. Ribosome (ko03010), amino sugar and nucleotide sugar metabolism (ko00520), ribosome biogenesis in eukaryotes (ko03008), circadian rhythm–plant (ko00270), and starch and sucrose metabolism (ko00500) were the top five KEGG terms with the highest p-value, enriching the most number of DEmRNAs. MS.gene53818 (MsUAM1) was considered to be the critical candidate gene for alfalfa response to cold stress by conjoint analysis of GWASs and DEmRNAs. A total of 223 DEmiRNAs, 1852 DElncRNAs, and 13 DEcircRNAs were identified under cold stress. Functional analysis indicates that they play important roles in GO terms such as leaf development (GO:0048366), DNA-binding transcription factor activity (GO:0003700), central vacuole (GO:0042807), response to auxin (GO:0009733), and water channel activity (GO:0015250), as well as in KEGG pathways such as plant hormone signal transduction, starch and sucrose metabolism, and flavone and flavonol biosynthesis (ko00944). A ceRNA network comprising 28 DElncRNAs, 8 DEcircRNAs, 11 DEmiRNAs, and 23 DEmRNA triplets was constructed. In this study, mRNAs and ncRNAs were identified that may be involved in alfalfa’s response to cold stress, and a ceRNA regulatory network related to cold stress was established, providing valuable genic resources for further research on the molecular mechanisms underlying alfalfa cold stress. Full article

Tibetan sheep, a unique breed indigenous to the Qinghai–Tibet Plateau, exhibit remarkable adaptations to high-altitude hypoxia, and their muscle quality is a key economic determinant. However, the molecular mechanisms by which exercise regulates meat quality in this breed remain poorly understood. This study aimed to systematically investigate the effects of different exercise volumes on the biceps femoris muscle of Tibetan sheep, integrating histological analysis with high-throughput transcriptome sequencing. We compared a low-exercise group with a high-exercise group and found that long-term endurance exercise resulted in phenotypic changes suggestive of a shift toward oxidative muscle fiber characteristics. This adaptation was characterized by significantly reduced muscle fiber diameter and cross-sectional area, alongside a crucial increase in intramuscular fat content, collectively enhancing meat tenderness, flavor, and juiciness. Transcriptomic analysis revealed extensive gene expression reprogramming, identifying 208 mRNAs and 490 lncRNAs that were differentially expressed and primarily associated with muscle fiber transition and energy metabolism. Furthermore, we constructed a putative lncRNA-miRNA-mRNA competing endogenous RNA network based on expression correlations and bioinformatic predictions, highlighting potential key regulatory axes such as LOC105603384/miR-16-z/MYLK3, LOC121820630/miR-381-y/NOX4, and LOC132659150/oar-miR-329a-3p/NF1. These findings provide a new perspective on the molecular basis of exercise-induced muscle adaptation in high-altitude animals and offer a solid theoretical framework for improving meat quality through scientific livestock management. Full article

Background and Aims: Androgenetic alopecia (AGA) represents the most prevalent multifactorial condition leading to hair loss, necessitating an enhanced molecular understanding. The aim of this study is to present the analysis integrating protein, mRNA and miRNA between frontal and occipital regions of patients with androgenetic alopecia (AGA) and to identify potential mechanism. Methods and Results: Paired frontal and occipital scalps from four male donors with AGA were collected for transcriptomic and proteomics analyses. The molecular and protein characteristics of AGA were demonstrated by a comprehensive bioinformatics approach. Additionally, immunofluorescence (IF) and dual-luciferase reporter (DLR) assays were employed to confirm the analytical findings. A total of 758 differentially expressed proteins (DEPs), 1802 differentially expressed mRNAs (DERs) and 61 differentially expressed miRNAs (DEmiRNAs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed significant enrichments in lipid metabolism, especially those involving PPAR signaling. Co-expression analyses further supported the association of up-regulated genes with lipid metabolism. A protein–protein interaction network analysis, supplemented by KEGG enrichment and the MCE algorithm, pinpointed four candidate genes: DBI, ACAA1, IDH1 and PEX3. IF confirmed significant upregulation of ACAA1 and PEX3 in scalp tissues with AGA, while IDH1 was downregulated and DBI without significant changes. A competing endogenous RNA network indicated that hsa-miR-1343-3p targets ACAA1 and hsa-miR-3609_R-2 targets IDH1, which were confirmed by DLR assays. Conclusions: This study provides preliminary evidence that hsa-miR-1343-3p-mediated regulation of ACAA1 contributes to AGA pathogenesis, suggesting a link between AGA and lipid metabolism. Full article

Silicosis is an irreversible and progressive pulmonary fibrotic disease caused by the long-term inhalation of silica dust. The precise molecular mechanisms underlying the disease remain incompletely understood, and effective early diagnostic biomarkers are still lacking. In this study, we used a silicosis mouse model and transcriptomic sequencing to identify 2950 mRNAs, 461 lncRNAs, 81 miRNAs, and 44 circRNAs that were differentially expressed in lung tissue. Enrichment analysis revealed that these differentially expressed genes were significantly enriched in the phosphatidylinositol 3-kinase (PI3K)–protein kinase B (Akt) signaling pathway, nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathway, and tumor necrosis factor (TNF) signaling pathway. The constructed competing endogenous RNA (ceRNA) network highlighted extensive regulatory interactions among lncRNAs/circRNAs, miRNAs, and mRNAs. Human validation showed that the expression levels of hsa-miR-215-5p and hsa-miR-146b-5p were significantly upregulated in the peripheral blood of early-stage pneumoconiosis patients, while hsa-miR-485-5p was downregulated. Logistic regression analysis revealed that hsa-miR-215-5p (OR = 1.966, 95% CI: 1.6938–2.2796, p < 0.001) and hsa-miR-146b-5p (OR = 1.9367, 95% CI: 1.697–2.201, p < 0.001) were independent risk factors for pneumoconiosis (p < 0.001). ROC curve analysis showed that both miRNAs demonstrated good diagnostic efficacy for pneumoconiosis, with AUC values of 0.9563 and 0.8876, respectively. These results provide novel insights into the complex ceRNA regulatory network involved in silicosis pathogenesis and suggest potential early, non-invasive diagnostic biomarkers. Full article

(1) Background: After HBV infection, viral transcripts and host RNA form a multi-layered interwoven regulatory network. However, a comprehensive map encompassing mRNA, miRNA, lncRNA, and circRNA is still lacking. This absence complicates the systematic explanation of the molecular mechanisms driving immune escape and metabolic reprogramming during the persistent infection stage. (2) Methods: In this study, we established a mouse model of chronic HBV infection and analyzed the differential expression of mRNA, miRNA, lncRNA, and circRNA through whole transcriptome sequencing (WTS). We constructed a competing endogenous RNA (ceRNA) network to systematically evaluate the overall impact of HBV on the host’s immune-metabolic pathways. (3) Results: RNA sequencing results indicated that HBV infection significantly up-regulated 194 mRNAs, 18 miRNAs, 184 lncRNAs, and 28 circRNAs, while down-regulating 42, 16, 122, and 31 corresponding transcripts, respectively. The differentially expressed genes were primarily enriched in pathways related to metabolism, immunity/inflammation, and signal transduction-ligand receptor interactions. Furthermore, the competitive endogenous RNA networks of lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA constructed on this basis further identified miR-185-3p as a key core node. (4) Conclusions: In this study, based on whole transcriptome data, the gene expression profiles of rcccDNA/Ad-infected Alb-Cre transgenic mice (chronic HBV infection model) and normal Alb-Cre mice were systematically compared, and the core regulatory factor miR-185-3p of key differentially expressed genes was screened. The microRNA is expected to provide a new target for the precise treatment of chronic hepatitis B by targeted intervention of viral replication and high liver inflammation. Full article

The open reading frame 3 (ORF3) protein of the swine hepatitis E virus (SHEV) is a critical virulence factor implicated in viral infection, yet its precise mechanisms remain poorly understood. Circular RNAs (circRNAs) have emerged as key regulators of gene expression during viral infections by functioning as miRNA sponges. This study aimed to identify key circRNAs and construct a potential circRNA-miRNA-mRNA regulatory network associated with the viral infection pathway in HepG2 cells expressing genotype IV SHEV ORF3. Based on our previous high-throughput circRNA and transcriptome sequencing data from HepG2 cells with adenovirus-mediated ORF3 overexpression, we screened for differentially expressed circRNAs and mRNAs linked to viral infection pathways. Using bioinformatic tools, we predicted miRNAs targeted by these mRNAs and those that could bind to the circRNAs, ultimately constructing a competing endogenous RNA (ceRNA) network with Cytoscape. We identified 31 differentially expressed circRNAs and 7 mRNAs (HSPA8, HSPA1B, EGR2, CXCR4, SOCS3, NOTCH3, and ZNF527) related to viral infection. A potential ceRNA network comprising 32 circRNAs, 23 miRNAs, and the 7 mRNAs was constructed. Core circRNAs, including ciRNA203, circRNA14936, and circRNA5562, may act as miRNA sponges to regulate the expression of these mRNAs. This network suggests a novel mechanism by which SHEV ORF3 might modulate host cell functions to facilitate viral infection. Full article

Small nucleolar RNAs (snoRNAs) and their host genes (SNHGs) are non-coding RNAs that are integral to tumorigenesis and progression. snoRNAs contribute to tumor progression primarily through RNA modification and engagement in intracellular signaling, and by serving as precursors for small nucleolar RNA-derived RNAs (sdRNAs) that exert microRNA (miRNA)-like or epigenetic regulatory functions. SNHGs modulate key tumor cell behaviors—including proliferation, metastasis, and resistance to therapy—through competing endogenous RNA (ceRNA)-mediated interactions and epigenetic mechanisms. Their combined influence significantly impacts patient prognosis. Across diverse malignancies such as neurologic, bone, and head and neck cancers, snoRNAs and SNHGs exhibit cancer-specific regulatory dynamics; for instance, in glioblastoma, snoRNAs and their derived fragments (sdRNAs) contribute to intratumoral heterogeneity by mediating both metabolic reprogramming and epigenetic remodeling, while their mediated modulation of cellular proliferation and metastatic potential is evident in breast cancer. Concurrently, several snoRNAs and SNHGs have emerged as potential diagnostic and prognostic biomarkers, as well as therapeutic targets. Preclinical interventions targeting select snoRNAs or SNHGs have demonstrated promising therapeutic outcomes. This study reviews current insights into the oncogenic functions and signaling networks associated with dysregulated snoRNAs and SNHGs in malignancies, while highlighting novel avenues for future investigation in this domain. Full article

Cervical cancer (CCa) is the fourth leading cause of cancer-related deaths among women worldwide, with nearly 90% of cases in low- and middle-income countries, especially in Sub-Saharan Africa. This study explores the roles of circular ribonucleic acids (circRNAs), hsa_circ_0001038 and circRNA_400029, and the impact of the serine/arginine-rich splicing factor 3 (SRSF3) inhibitor, theophylline, in CCa cell lines. We utilized cell cycle fluorescence-activated cell sorting (FACS) and Annexin V/propidium iodide (PI) assays to evaluate theophylline’s effects on SiHa and C33A cell lines. Results showed S-phase arrest in SiHa and G2/M arrest in C33A, with significant cytotoxic effects indicated by apoptosis analysis. Using CircAtlas, we identified micro ribonucleic acids (miRNAs) binding to hsa_circ_0001038, particularly miR-205-5p, which has a tumour-suppressive role. miRTarBase identified miR-16-5p as a key interacting miRNA for circRNA_400029. We constructed a competing endogenous ribonucleic acid (ceRNA) network, revealing multiple miRNA targets. Pathway analysis via the Kyoto Encyclopedia of Genes and Genomes (KEGG) highlighted critical signalling pathways involved in CCa oncogenesis. In conclusion, theophylline demonstrates cytotoxicity in CCa cells, suggesting its potential for repurposing in CCa theranostics, though further optimization is necessary. Full article

Background: Non-small cell lung cancer (NSCLC) progression is driven by dysregulated competing endogenous RNA (ceRNA) networks, where non-coding RNAs sequester miRNAs to modulate oncogene expression. The tumor-suppressor miR-145 is frequently downregulated in NSCLC, but its lncRNA-mediated regulation remains incompletely characterized. Methods: Integrated transcriptomic analysis of NSCLC datasets (GSE135304: blood RNA from 712 patients; GSE203510: plasma miRNAs) was used to identify dysregulated genes (|log2FC| > 0.1, p < 0.05) and miRNAs (|log2FC| > 1, p < 0.05). Experimentally validated targets from miRTarBase/TarBase were intersected with dysregulated genes, followed by WikiPathways/GO enrichment. ceRNA networks were constructed via co-expression analysis. RT-qPCR validated miR-145-3p expression in A549/MRC-5 cells and NSCLC tissues. GEPIA assessed FN1/CCND1 clinical relevance. Results: We identified 8271 dysregulated genes and 52 miRNAs. miR-145-3p, critical in immune regulation, was significantly downregulated (log2FC = −1.24, p = 0.036). Intersection analysis revealed 27 miR-145-3p targets (e.g., FN1, CCND1, SMAD3) enriched in immune pathways (FDR < 0.05) and TGF-β-mediated EMT within the dysregulated geneset. Six immune-linked hub genes emerged. LncRNAs LOC729919 and LOC100134412 showed strong co-expression with hub genes and competitively bind miR-145-3p, derepressing the expression of the metastasis drivers FN1 (ECM regulator) and CCND1 (cell cycle controller). This ceRNA axis operates within a broader dysregulation of ATM-dependent DNA damage, Hippo signaling, and cell cycle pathways. RT-qPCR confirmed significant miR-145-3p suppression in NSCLC models (p < 0.05). GEPIA revealed a significant FN1-CCND1 co-expression (p = 0.0017). Conclusions: We characterize a novel LOC729919/LOC100134412–miR-145–FN1/CCND1 ceRNA axis in NSCLC pathogenesis. FN1’s prognostic value and functional linkage to CCND1 underscores its potential clinical relevance for therapeutic disruption. Full article

Background: Tissue-specific long non-coding RNAs (lncRNAs) represent potential biomarkers. The testis-enriched lncRNA41584, previously identified as downregulated in male-sterile silkworm mutants (JMS, GMS), is associated with male sterility, but its functional mechanism remained unknown. Subcellular localization, dual-luciferase reporter assays, MTT, and flow cytometry were employed to examine lncRNA41584–miR-3047-z–BmCDK20 interactions. In vivo functional validation included lncRNA41584 knockdown and miR-3047-z overexpression in Bombyx mori. lncRNA41584 localizes predominantly to the cytoplasm and acts as a competing endogenous RNA (ceRNA) by sponging miR-3047-z, thereby upregulating the cyclin-dependent kinase BmCDK20. Perturbation of this axis impaired BmN cell proliferation, causing G1 phase arrest, and led to spermatocyst malformation, reduced fertilization rates, and increased unfertilized eggs. The lncRNA41584–miR-3047-z–BmCDK20 ceRNA network is essential for testicular cell cycle progression and spermatogenesis in silkworms, offering mechanistic insights into lepidopteran male sterility and potential targets for pest fertility regulation. Full article

Cold stress reduces horticultural crop yield and postharvest quality by disrupting membrane fluidity, redox equilibrium, and the cell wall structure. This results in chilling injury, tissue softening, and loss of color. Long noncoding RNAs (lncRNAs) have emerged as key integrators of plant cold signaling pathways. LncRNAs mediate the interaction between calcium signaling systems and transcriptional cascades while coordinating hormone signaling networks, including those involving abscisic acid, jasmonic acid, ethylene, salicylic acid, and brassinosteroids. LncRNAs influence gene regulation through chromatin-based guidance, sequestration of repressive complexes, natural antisense transcriptional interference, microRNA-centered competing endogenous RNA networks, and control of RNA splicing, stability, localization, and translation. Studies in horticultural species revealed that cold-responsive lncRNAs regulate processes essential for fruit firmness, antioxidant levels, and shelf-life, including lipid modification, reactive oxygen species balance, and cell wall or cuticle remodeling. This review aims to summarize tissue- and developmental stage-specific expression patterns and highlight experimental approaches to validate RNA function, including gene editing, transcript recovery, advanced sequencing, and analysis of protein-RNA interactions. Integrating these results will facilitate the development of precise molecular markers and nodes of regulatory networks that increase cold tolerance, and improve the quality of horticultural crops. Full article