Search Results (8,594)

Acute lymphoblastic leukemia (ALL) is a clinically diverse cancer in which microRNA (miRNA)-mediated post-transcriptional regulation contributes to leukemogenesis and subtype heterogeneity. In this study, miRNA expression profiling by microarray was performed on ALL cases (B-ALL and T-ALL) and healthy controls. Data were normalized and analyzed for differential expression using false discovery rate (FDR)-adjusted p-values. Differentially expressed miRNAs were further examined using unsupervised visualization to assess overall disease-related expression patterns. To explore their biological significance, experimentally validated miRNA–target interactions were obtained using multiMiR, limited to validated databases (miRTarBase, TarBase, and miRecords) and summarized via target-burden ranking, miRNA–target network analysis, and Circos–style interaction mapping. A unique miRNA expression signature was identified in ALL. Upregulated miRNAs included miR-106a-5p, miR-106b-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-181b-5p, and miR-128-3p, while miR-127-3p, miR-139-5p, miR-433-3p, and miR-584-5p were downregulated. Validated targets concentrated on key leukemia-related genes like PTEN, BCL2L11, CDKN1A, CCND1, RB1, E2F1, and TGFBR2. KEGG pathway analysis highlighted pathways associated with leukemic cell survival and growth, including MAPK, cell cycle, autophagy, Hippo, ubiquitin-mediated proteolysis, and mTOR signaling pathways. These findings reveal a concise ALL-associated miRNA panel predominantly comprising the miR-17/20/106 family and provide a prioritized set of candidate regulatory networks for subtype-specific validation and functional follow-up studies. Full article

Chinese tongue sole (Cynoglossus semilaevis), an economically important mariculture species in China, exhibits pronounced sexual dimorphism in growth, underscoring the importance of elucidating sex regulatory mechanisms for aquaculture development. Heterogeneous nuclear ribonucleoprotein K (hnrnpk) critically regulates mammalian reproductive development, yet its role in fish sex regulation remains elusive. Here, we systematically investigated the underlying function and mechanisms of hnrnpk in C. semilaevis through integrated molecular cloning, expression profiling, upstream regulatory analysis, functional assays, and transcriptome sequencing. We found that hnrnpk was highly expressed in the gonad and liver, with female-biased expression during gonadal development. Promoter activity assays revealed that sox2 and c-Jun enhanced hnrnpk transcription, whereas foxl2 and ar suppressed it. Additionally, hnrnpk was directly targeted by miR-460a-5p in C. semilaevis, revealing multi-level transcriptional and post-transcriptional regulation. Functional analyses showed that hnrnpk regulated cyp19a1a in a cell type-dependent and dose-sensitive manner: the expression of cyp19a1a was both upregulated in hnrnpk-knockdown ovarian cells and hnrnpk-overexpression testicular cells. Interestingly, foxl2 was upregulated in hnrnpk-knockdown ovarian cells but suppressed in hnrnpk-overexpression testicular cells, which showed the distinct regulation mechanisms in the different sexual programs. Transcriptomic analyses further revealed that several sex-related genes (sox9a with downregulation, etc.) were significantly regulated, and cell development and cycle pathways were dramatically enriched in functional enrichment analyses. This might indicate that hnrnpk overexpression drives C. semilaevis testis (CSTE) toward feminization reprogramming through sox9 switching and multi-pathway perturbations. Overall, our findings might reveal that hnrnpk, a female-biased gene regulated by miR-460a-5p and transcription factors, influences sex-related gene expression through sox9 switching. This study will offer new insights for C. semilaevis hnrnpk into sex determination and also provide a potential target for monosex breeding in aquaculture. Full article

Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease affecting the axial skeleton, characterized by progressive structural damage and functional impairment. Although biologic therapies targeting tumor necrosis factor and interleukin-17 have improved clinical outcomes, a substantial proportion of patients fail to achieve sustained disease control. Emerging evidence suggests that metabolic alterations may contribute to AS pathogenesis; however, systematic characterization of metabolism-related biomarkers and their regulatory networks remains limited, and the interplay between metabolic dysfunction and immune dysregulation in AS is poorly understood. Two whole-blood GEO datasets (GSE25101, GSE73754; n = 104) were integrated as the primary analytical cohort. A third dataset (GSE11886, n = 18; monocyte-derived macrophages) was included for exploratory cross-tissue analysis. Differential expression analysis identified 847 DEGs, which were refined to 16 metabolism-related genes through weighted gene co-expression network analysis (WGCNA) and GeneCards database filtering. Eleven machine learning algorithms with 5-fold cross-validation were applied to construct diagnostic models and identify hub genes. Validation analyses included immune cell infiltration estimation using CIBERSORT, metabolic pathway activity assessment via ssGSEA, single-cell transcriptomics from GSE268839, functional enrichment through GSEA/GSVA, and chromosomal localization analysis. A competing endogenous RNA (ceRNA) regulatory network was constructed to map post-transcriptional regulation. Natural compounds from 66 AS-treating traditional Chinese medicines were screened against hub genes using deep learning-based binding prediction. Multiple machine learning algorithms achieved comparable cross-validated performance (CV AUC range 0.741–0.836; top five models: 0.805–0.836) using the six hub genes (MFN2, SLC27A3, RHOB, SMG7, AKR1B1, LCOR) identified through SHAP-based feature importance analysis of the PLS model. Leave-one-dataset-out validation between the two whole-blood cohorts showed that all algorithms exceeded an AUC of 0.77 in Round 1 (validate: GSE73754, n = 72; best AUC 0.861), while Round 2 (validate: GSE25101, n = 32) yielded more modest performance (best AUC, 0.715) reflecting the smaller validation sample. Exploratory application to GSE11886 (macrophage-derived samples) showed near-chance performance, consistent with the tissue-source discrepancy. AS patients exhibited significant downregulation of oxidative phosphorylation, TCA cycle, and glycolysis pathways (p < 0.01), accompanied by elevated glutathione metabolism (p < 0.001). Immune cell deconvolution revealed reduced CD8+ T cell proportions correlating with MFN2 downregulation, and increased neutrophil frequencies correlating with SLC27A3 upregulation. Exploratory single-cell analysis indicated that RHOB expression was relatively enriched in border-associated macrophages and fibroblasts, while AKR1B1 was more prominently expressed in vascular endothelial cells and plasmacytoid dendritic cells. The ceRNA network identified 21 miRNAs and 65 lncRNAs forming 86 regulatory interactions, with four key regulatory axes (SATB1-AS1/miR-539-5p/LCOR, FAM95B1/miR-223-3p/RHOB, LINC01106/miR-106a-5p/MFN2, AATBC/miR-185-5p/SMG7) predicted to regulate hub gene expression. Compound screening identified betaine, pyruvic acid, citric acid, etc., as top-ranking candidates, with MFN2 showing the highest binding capacity among hub genes. This study provides an integrative framework linking metabolic reprogramming with immune dysfunction in AS. The six-gene diagnostic signature showed preliminary discriminatory ability in the available datasets, while the ceRNA regulatory network and natural compound screening results prioritize candidate regulatory pathways and compounds for future validation. These findings advance our understanding of AS pathogenesis and may guide future biomarker development and targeted intervention strategies. Full article

Glioblastoma (GBM) remains one of the most lethal and treatment-resistant human malignancies, characterized by extreme molecular heterogeneity and a highly immunosuppressive tumor microenvironment (TME). MicroRNAs are a set of small endogenous non-coding RNA molecules which play critical roles in various biological processes including carcinogenesis. Recent evidence identifies microRNA-10b (miR-10b) as a regulator of gliomagenesis, with glioblastoma exhibiting a unique state of “oncogene addiction” to this molecule. This review summarizes current research on the mechanistic roles of miR-10b in GBM tumor progression and immune evasion, evaluates innovative antisense oligonucleotide delivery systems, and explores the clinical potential of combining miR-10b inhibition with standard-of-care treatments. Full article

Circular RNAs (circRNAs) have been reported to be closely associated with tumor progression in multiple malignancies. However, the specific mechanism by which circPRKCA influences tumor progression has not been fully elucidated. CircPRKCA is highly expressed in non-small cell lung cancer (NSCLC) tissues and cells. Knockdown of circPRKCA inhibits the malignant behaviors of NSCLC cells. RNA sequencing results revealed that FRMD6 and SNAI2 mRNAs are positively correlated with circPRKCA. Subsequently, we proved that circPRKCA acts as a molecular sponge for miR-200b-3p. Additionally, miR-200b-3p binds to the 3′ untranslated regions (3′UTRs) of FRMD6 and SNAI2 mRNAs to promote their degradation. Overexpression of circPRKCA thereby suppresses this degradation process and coun-teracts the tumor-suppressive effects induced by miR-200b-3p. CircPRKCA functions as the sponge of miR-200b-3p, suppressing the SNAI2/FRMD6 mRNA degradation driven by miR-200b-3p and accelerating NSCLC progression. Full article

This study aimed to investigate the molecular mechanisms underlying dopaminergic injury induced by gestational and lactational atrazine (ATR) exposure in rat offspring, with a particular focus on non-coding RNA-mediated regulation. Pregnant rats were exposed to ATR during gestation and lactation. Offspring underwent behavioral testing at postnatal day 21 (PND21) and were sacrificed for midbrain tissue collection at PND28. Behavioral alterations, histopathological changes in the substantia nigra, and dopaminergic marker expression were assessed to evaluate ATR-induced neurotoxicity. Whole-transcriptome sequencing was then performed to identify differentially expressed mRNAs, miRNAs, and lncRNAs, followed by co-expression, protein–protein interaction, and competing endogenous RNA (ceRNA) network analyses. Key targets were validated by qRT-PCR. Candidate molecules identified from transcriptomic and ceRNA analyses were further examined in an ATR-induced neurotoxicity model established in RA-differentiated SK-N-SH cells. Dual-luciferase reporter, Ago2-RNA immunoprecipitation, and biotin-labeled RNA pull-down assays were used to examine putative binding relationships and molecular interactions. In addition, lentivirus-mediated Elavl4 overexpression was performed to further evaluate the role of this candidate regulator in ATR-induced Nurr1 downregulation. Gestational and lactational ATR exposure induced significant behavioral abnormalities in rat offspring. These changes were accompanied by histopathological alterations in the substantia nigra, including reduced TH immunoreactivity, as well as abnormal expression of dopaminergic markers, characterized by decreased TH and Nurr1 levels and increased α-syn expression. Together, these findings indicate the presence of dopaminergic injury. Whole-transcriptome analysis further revealed widespread dysregulation of mRNAs, miRNAs, and lncRNAs in ATR-exposed offspring. Subsequent integrative analysis suggested a potential ceRNA regulatory relationship among Elavl4, miR-301a-5p, and Nurr1, which was further supported by qRT-PCR. Dual-luciferase reporter, RIP, and RNA pull-down assays supported direct interactions between miR-301a-5p and both Elavl4 and Nurr1, as well as their association with the Ago2-containing silencing complex. Moreover, Elavl4 overexpression partially reversed ATR-induced Nurr1 downregulation in vitro. Gestational and lactational ATR exposure induced behavioral abnormalities and dopaminergic injury in rat offspring. Whole-transcriptome analysis combined with experimental validation suggests a potential association between the Elavl4/miR-301a-5p/Nurr1 ceRNA axis and ATR-induced dopaminergic injury, providing insight into the post-transcriptional mechanisms underlying developmental neurotoxicity. Full article

Background: Lung cancer ranks among the most common and deadly malignant tumors worldwide. Drug resistance is a critical factor hindering the effect of chemotherapy for lung cancer. Exosomes, as intercellular signaling molecule carriers, play an important role in carcinogenesis, metastasis and drug resistance. Our study was aimed at exploring the impact of exosomes derived from docetaxel (DTX)-resistant lung cancer cells on regulating biological behaviors of DTX-sensitive cells, further investigating the molecular mechanisms regarding exosome-mediated intercellular communication. Methods: We extracted and identified the exosomes derived from A549, A549/DTX, H1299 and H1299/DTX cells, and then analyzed the expression of exosomal miR-373-3p between DTX-sensitive and DTX-resistant cells. Cell proliferation and apoptosis experiments were verified using a CCK-8 assay, a colony formation assay, a TUNEL assay and flow cytometry. The molecular interaction between miR-373-3p and PDCD4 was evaluated using a dual-luciferase reporter assay. The function of miR-373-3p was further assessed using an in vivo mouse xenograft model. Results: We found that the exosomal miR-373-3p level from DTX-resistant A549/DTX or H1299/DTX cells significantly exceeded that from DTX-sensitive A549 or H1299 cells. In addition, both exosomes derived from DTX-resistant lung cancer cells and miR-373-3p mimics could promote the proliferation of DTX-sensitive cells and inhibit their apoptosis. Moreover, we identified PDCD4 as a key target gene of miR-373-3p, which could induce the malignant behaviors of DTX-sensitive cells by reducing PDCD4 expression. Conclusions: Our results demonstrated that DTX-resistant lung cancer cells could transfer miR-373-3p to DTX-sensitive cells through exosomes, where miR-373-3p could exert its carcinogenic effect via targeting PDCD4. Full article

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer and remains a leading cause of cancer-related mortality worldwide. MicroRNAs (miRNAs) are critical regulators of tumor progression; however, the biological role and molecular mechanisms of miR-589-3p in LUAD remain unclear. In this study, the expression levels of miR-589-3p and WWC2 were analyzed using The Cancer Genome Atlas lung adenocarcinoma (TCGA-LUAD) datasets via the UALCAN platform. Flow cytometric apoptosis analysis and functional assays including CCK-8, colony formation, AO/EB staining, and Transwell invasion assays were performed in LUAD cell lines. The interaction between miR-589-3p and WWC2 was validated using dual-luciferase reporter assays, Western blotting, and rescue experiments. miR-589-3p expression was significantly elevated in LUAD tissues compared with normal lung tissues (p < 0.05) and was positively associated with an advanced tumor stage and lymph node metastasis (p < 0.05). Inhibition of miR-589-3p significantly suppressed proliferation and colony formation (p < 0.05), reduced invasive capacity (p < 0.05), and markedly increased apoptosis (p < 0.01) in LUAD cells. Dual-luciferase reporter assays confirmed WWC2 as a direct target of miR-589-3p, with miR-589-3p mimics significantly reducing WWC2 wild-type reporter activity (p < 0.05). WWC2 expression was significantly downregulated in LUAD tissues (p < 0.05), and WWC2 knockdown reversed the anti-proliferative, pro-apoptotic, and anti-invasive effects induced by miR-589-3p inhibition (p < 0.01). These findings demonstrate that miR-589-3p promotes lung adenocarcinoma progression by directly suppressing WWC2. The miR-589-3p/WWC2 axis represents a novel molecular mechanism contributing to LUAD malignancy and may provide a foundation for future mechanistic and translational studies. Full article

2,3′,4,4′,5-Pentachlorobiphenyl (PCB118) is a persistent environmental pollutant associated with adverse female reproductive outcomes; however, its effects on uterine function and epigenetic regulation remain incompletely understood. This study investigated whether PCB118 disrupts uterine decidualization and angiogenesis through miRNA-mediated regulatory pathways. Human endometrial stromal cells (HESCs) and human umbilical vein endothelial cells (HUVECs) were exposed to an environmentally relevant, non-cytotoxic concentration of PCB118. Decidualization and angiogenesis were evaluated in vitro, and underlying mechanisms were investigated using molecular and miRNA-based approaches. In vivo validation of miR-542-3p expression was performed in pregnant mice following PCB118 exposure. PCB118 exposure was associated with reduced expression of decidualization markers, including prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP-1), as well as impaired angiogenic capacity in HUVECs. PCB118 treatment was accompanied by increased miR-542-3p expression, which was associated with decreased integrin-linked kinase (ILK) levels and changes in transforming growth factor beta 1 (TGF-β1) and total Smad2 protein abundance. ILK overexpression partially restored decidualization and angiogenesis-related phenotypes, supporting a functional involvement of ILK in these processes. Consistently, elevated miR-542-3p expression was observed in murine endometrial tissues following PCB118 exposure, suggesting physiological relevance in vivo. PCB118 exposure is associated with impaired decidualization and angiogenesis, potentially involving dysregulation of the miR-542-3p/ILK signaling axis, suggesting a potential role for epigenetic modulation in PCB118-associated reproductive dysfunction. Full article

Background/Objectives: MicroRNAs (miRNAs) are key regulators of gene expression and have been implicated in multiple aspects of cancer progression. However, the role of miR-214-3p in breast cancer remains controversial. In this study, we investigated the functional role of miR-214-3p and explored its potential regulatory target in breast cancer, particularly in triple-negative breast cancer (TNBC). Methods: miR-214-3p expression was evaluated in breast cancer cell lines. Luciferase reporter assays were performed to assess functional targeting of the FRK 3′-UTR. Functional assays, including proliferation, migration, and invasion assays, were conducted following miR-214-3p overexpression or FRK silencing. Results: miR-214-3p was markedly upregulated in TNBC cells (MDA-MB-231), while Fyn-related kinase (FRK), a potential tumor suppressor, showed an inverse expression trend. Luciferase reporter assays demonstrated that miR-214-3p functionally targets the 3′-UTR of FRK. Functional analyses revealed that overexpression of miR-214-3p significantly increased cell proliferation, migration, and invasion. Notably, silencing of FRK recapitulated these effects, supporting its role as a functional mediator of miR-214-3p. Conclusions: This study identifies a miR-214–FRK regulatory axis in breast cancer and suggests its contribution to aggressive tumor behavior. Targeting miR-214-3p or modulating FRK activity may represent a potential therapeutic strategy. Full article

Background: Recurrence poses a major challenge in epithelial ovarian cancer (EOC), often occurring despite optimal first-line therapy. Dormant cancer cells are believed to play a key role, yet the mechanisms driving their reactivation remain unclear. This study examined whether exosomes released by normal peritoneal mesothelial cells (PMCs) and fibroblasts (PFBs) undergoing iatrogenic senescence after carboplatin and paclitaxel exposure contribute to EOC recurrence. Methods and Results: Senescent PMCs and PFBs secreted markedly more exosomes, identified by CD9, CD63, and CD81, compared with young cells. Exosomes from both cell types more effectively reactivated dormant EOC cells (pEOCs, A2780, OVCAR-3, SKOV-3) than non-exosomal medium constituents. Importantly, senescent PMC-derived exosomes most strongly reactivated pEOCs and SKOV-3, whereas those from senescent PFBs exerted greater effects on pEOCs, OVCAR-3, and SKOV-3. Kinetic studies of exosome internalization revealed that this process was generally more efficient in the presence of exosomes derived from senescent cells compared with those from young donor cells. Compositional analysis revealed distinct profiles between young and senescent exosomes compared in two variants: young PMCs/senescent PMCs and young PFBs/senescent PFBS. Senescent PMC exosomes displayed reduced miR-210-3p, miR-409-3p, and miR-421, alongside elevated MMP1, MMP3, and VEGF, while senescent PFB exosomes showed increased amphiregulin and osteopontin but lower MMP1, MMP3, TIMP1, bFGF, VEGF, and HGF. Functionally, senescent PMC exosomes enhanced pEOC migration, invasion, and spheroid formation, and induced the expression of CCL11 and ABCB1. Senescent PFB exosomes promoted migration and upregulated CCL11, TGF-β1, BIRC5, and CHEK1. Conclusions: These findings suggest that therapy-induced senescence in peritoneal cells may contribute to EOC recurrence by reactivating dormant tumor cells through exosomal signaling. Full article

Background: Foster adolescents face elevated socioemotional risk, yet the joint and differential contributions of family adversity, attachment insecurity, and relational trauma to distinct adjustment domains remain poorly understood. The present study aimed to examine their joint, incremental, and differential contribution to emotional regulation difficulties and social competence. Methods: Forty-six adolescents (12–17 years; 63% female) in residential care in Uruguay completed self-report measures of family problems, attachment dimensions (anxiety, avoidance, socioemotional functioning), and relational trauma (SENA, CAA-R, CaMir-R). Hierarchical multiple regression examined their sequential prediction of emotional regulation difficulties and social competence. Results: Emotional regulation difficulties were explained by family problems, avoidant attachment, and relational trauma, whereas social competence was explained by anxious attachment and socioemotional attachment functioning. Final models explained 49% and 47% of variance, respectively. Discussion: This differential predictive pattern aligns with theoretical distinctions between deactivating and hyperactivating attachment strategies. Relational trauma’s specific contribution to regulatory, but not social, functioning supports neurobiologically grounded models of complex trauma. Conclusions: Findings suggest that emotional regulation difficulties were more closely associated with family problems, avoidant attachment, and relational trauma, whereas social competence was more strongly linked to anxious attachment and socioemotional attachment functioning. These results support differentiated, attachment-informed, and trauma-sensitive approaches in residential care settings. Full article

Acute myocardial infarction (AMI) causes high mortality, with cardiomyocyte apoptosis playing a critical role. Although circular RNAs modulate cardiac disorders, related mechanisms remain unclear. Here, we identify circRERE as a previously unrecognized pro-apoptotic regulator under ischemic stress. circRERE is markedly upregulated in ischemic myocardium and promotes apoptosis by sponging miR-27a-3p to elevate Caspase9. Using epigallocatechin gallate-primed exosomes (EGCG-primed exosomes, Exo^EGCG) as a tool to modulate circRERE, we found that Exo^EGCG significantly reduced circRERE levels, restored miR-27a-3p activity, and suppressed Caspase9. Gain- and loss-of-function tests confirmed that circRERE mediates Exo^EGCG-derived protection. Collectively, circRERE represents a novel and actionable target for AMI, with Exo^EGCG serving as an effective delivery platform. Full article

This study presents a comparative evaluation of multiple-approach optical spectroscopic sensor—Laser-Induced Breakdown Spectroscopy (LIBS), Mid-Infrared Spectroscopic sensing (MIRS), and Hyperspectral Imaging (HSI)-based sensors operating in the Visible–Near-Infrared (VNIR) and Short-Wave Infrared (SWIR) ranges—for the quantitative detection of calcium carbonate (CaCO₃) in pelletized CaCO₃-CaO mixtures. The objective was to assess and compare the sensing performance of these optical sensor platforms for carbonate quantification. Each spectroscopic sensor dataset was processed using chemometric calibration methods, including Partial Least Squares Regression (PLSR), to ensure robust and reproducible quantitative predictions. Although the samples consisted of binary CaCO₃-CaO mixtures, the sensing task focused exclusively on CaCO₃ content. Results indicate that LIBS, MIRS, and HSI-SWIR-based sensing approaches achieved comparable quantitative performance, with LIBS providing the highest prediction accuracy. In contrast, the HSI-VNIR sensor configuration demonstrated lower predictive capability relative to the other optical sensing modalities. These findings highlight the potential and limitations of different optical sensor technologies for carbonate detection in heterogeneous mineral systems. Full article

Our previous work demonstrated that bovine milk-derived extracellular vesicles (mEVs) could alleviate the inflammatory response of mice colitis, along with hundreds of differentially expressed (DE) mRNAs. This study further analyzed the profiles of non-coding RNAs (ncRNAs) and explored the correlation with DE mRNAs by constructing ceRNA networks. Six-week-old male C57BL/6 mice were fed either a control diet or a diet added with mEVs for 30 days. Then the mice were given dextran sulphate sodium in drinking water for 7 days to induce colitis. A total of 40 miRNAs, 541 lncRNAs and 643 circRNAs exhibited changes in mEVs pretreatment group. Among these DE miRNAs, mEVs pretreatment significantly increased the expressions of miR-122, miR-147, miR-210, miR-1224, miR-148a, and miR-212, which might participate in the inflammatory response of the colitis models. The expression of Tug1 increased after mEVs pretreatment, while Snhg5 and H19 decreased, which might be involved in intestinal barrier restoration. Functional analysis of the DE ncRNAs suggested mEVs might exert protective effects not only through modulation of inflammatory responses but also by enhancing intestinal stem cell function and epithelial regeneration, which were mainly regulated by Wnt and Hippo signaling pathways according to the ceRNA networks. Full article