Search Results (4,181)

Background: Myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) are clonal hematological disorders that share molecular origins but present with distinct clinical features. MicroRNAs (miRNAs) are key post-transcriptional regulators, and their altered expression may reflect biological shifts contributing to disease progression. Methods: Expression levels of miR-155, miR-181, miR-221, miR-222, and miR-223 were analyzed by RT-qPCR in bone marrow samples from 37 MDS patients, 20 AML patients, and 7 controls. Group comparisons were performed using ANOVA (with Benjamini–Hochberg correction) and Tukey post hoc testing. Diagnostic performance and network behavior were evaluated using ROC analysis, Pearson correlation matrices, and principal component analysis (PCA). Results: miR-155, miR-181, and miR-223 were upregulated in AML, whereas miR-221 and miR-222 were downregulated. miR-222 showed the highest diagnostic accuracy (AUC ~0.87 for both AML vs. control and MDS vs. control). Its expression was significantly higher in high IPSS-R MDS cases (p = 0.046), with a similar upward tendency for miR-221 (p = 0.054). Progressive loss of coordinated miRNA expression was observed from controls to MDS and AML. PCA supported these findings by showing separation mainly driven by miR-222 and miR-155. Conclusions: Combined miRNA profiling highlights miR-222 and, to a lesser extent miR-155, as consistent indicators of myeloid disease transformation. While further validation in larger and genetically stratified cohorts is warranted, these findings support the potential contribution of miRNA signatures to diagnostic evaluation and risk stratification in MDS and AML, in line with precision hematology approaches. Full article

Background: Transposable elements are normally silenced by epigenetic mechanisms; however, during malignant transformation, epigenetic alterations enable transposons to produce functional molecules like miRNAs. Among these, LINE-2 (L2) elements can generate miRNAs capable of regulating key genes, including tumor suppressors. Two L2-derived miRNAs, miR-28 and miR-708, have been linked to lung cancer, yet the mechanisms underlying their dysregulation remain poorly understood. Our study reveals how genomic context contributes to aberrant gene expression through comprehensive bioinformatic analyses. Methods: Using bioinformatics analysis, we evaluated the expression of miR-28 and miR-708 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) datasets from TCGA. Further, we assessed the expression and methylation status of miR-28 and miR-708 host genes, LPP and TENM4, respectively, TENM4 using computational tools. Finaly, we searched for potential candidate tumor suppressor genes targeted by miR-28 and miR-708, which are downregulated in LUAD and LUSC. Results: We found that intragenic L2-derived miR-28 and miR-708 are significantly upregulated in LUAD and LUSC. While TENM4 gene also displays a marked increase in expression in LUAD and LUSC, in tumor versus normal tissue, this difference is less obvious for the LPP gene. We suggest that such dysregulations in expression might be linked to specific methylation patterns of their genomic locations. Furthermore, we emphasize that miR-28 and miR-708 might contribute to lung cancer pathogenesis by targeting key tumor suppressor genes. Conclusions: Alterations in the methylation status of L2-miRNAs genomic loci might result in elevated levels of miRNAs and subsequent targeting of tumor suppressor genes with potential implications in lung cancer pathogenesis. Full article

Background: HER2-positive breast cancer patients receiving chemotherapy and targeted therapy (including anthracyclines and trastuzumab) face an elevated risk of cardiotoxicity, which can lead to long-term cardiovascular complications. Identifying predictive biomarkers is essential for early intervention. Circulating microRNAs (miRNAs), known regulators of gene expression and cardiovascular function, have emerged as potential indicators of cardiotoxicity. This study aims to evaluate the differential expression of circulating miRNAs in HER2-positive breast cancer patients undergoing chemotherapy and to assess their prognostic ability for therapy-induced cardiotoxicity using machine learning models. Methods: Forty-seven patients were assessed for cardiac toxicity at baseline and every 3 months, up to 15 months. Blood samples were collected at baseline. MiRNA expression profiling for 84 microRNAs was performed using the miRCURY LNA miRNA PCR Panel. Differential expression was calculated via the 2−∆∆Ct method. The five most upregulated and five most downregulated miRNAs were further assessed using univariate logistic regression and receiver operating characteristic (ROC) analysis. Five machine learning models (Decision Tree, Random Forest (RF), Support Vector Machine (SVM), Gradient Boosting Machine (GBM), k-Nearest Neighbors (KNN)) were developed to classify cardiotoxicity based on miRNA expression. Results: Forty-five miRNAs showed significant differential expression between cardiac toxic and non-toxic groups. ROC analysis identified hsa-miR-155-5p (AUC 0.76, p = 0.006) and hsa-miR-124-3p (AUC 0.75, p = 0.007) as the strongest predictors. kNN, SVM, and RF models demonstrated high prognostic accuracy. The decision tree model identified hsa-miR-17-5p and hsa-miR-185-5p as key classifiers. SVM and RF highlighted additional miRNAs associated with cardiotoxicity (SVM: hsa-miR-143-3p, hsa-miR-133b, hsa-miR-145-5p, hsa-miR-185-5p, hsa-miR-199a-5p, RF: hsa-miR-185-5p, hsa-miR-145-5p, hsa-miR-17-5p, hsa-miR-144-3p, and hsa-miR-133a-3p). Performance metrics revealed that SVM, kNN, and RF models outperformed the decision tree in overall prognostic accuracy. Pathway enrichment analysis of top-ranked miRNAs demonstrated significant involvement in apoptosis, p53, MAPK, and focal adhesion pathways, all known to be implicated in chemotherapy-induced cardiac stress and remodeling. Conclusions: Circulating miRNAs show promise as biomarkers for predicting cardiotoxicity in breast cancer patients. Machine learning approaches may enhance miRNA-based risk stratification, enabling personalized monitoring and early cardioprotective interventions. Full article

Over the years, there has been extensive research conducted on Parkinson’s Disease (PD), a neurodegenerative disorder known for causing motor impairment and behavioral changes. In more recent years, the roles of dysregulated microRNAs (miRNAs) in PD pathology have been studied in the hopes of developing new diagnostic methods or even treatments. This systematic review pinpoints and examines studies between 2010 and 2024 that have identified significant dysregulation of miRNAs in patients with PD. Upon filtering out the search results by a series of exclusion criteria, this review was conducted using 56 relevant studies. These studies revealed a vast array of significantly dysregulated miRNAs identified in the samples of patients with PD, when compared to healthy controls. A number of these miRNAs, such as miR-29c-3p, are likely biomarkers for more accurate PD diagnosis, and many, such as miR-485-3p, were found to be involved in PD pathogenesis. With further research, miRNAs could become a helpful diagnostic and prognostic tool for PD, with some of them even being candidate therapeutic targets for future treatments. Full article

Background: MicroRNAs (miRNAs) such as miR-155-5p and miR-221-3p are key regulators of gene expression in cancer. Although both have been implicated in colorectal cancer (CRC) and papillary thyroid carcinoma (PTC), data on their regional expression profiles and clinical associations remain scarce, particularly in the Middle East. This study assessed the expression patterns and clinical relevance of miR-155-5p and miR-221-3p in CRC and PTC patients from Sulaymaniyah Province, Iraq. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor and adjacent normal tissue samples were collected from 60 CRC patients and 50 PTC patients. miRNA expression levels were quantified using real-time quantitative PCR (RT-qPCR) and analyzed by the ΔΔCt method, adjusted for tumor cellularity. Statistical analyses were conducted to evaluate associations between miRNA expression and clinicopathological parameters. Results: miR-155-5p and miR-221-3p were frequently overexpressed in both CRC (65%) and PTC (72% and 68%, respectively). In CRC, miR-155-5p expression correlated significantly with histological grade, tumor location, and TNM stage (p < 0.05), while miR-221-3p did not show significant associations with clinicopathological features. In PTC, miR-155-5p exhibited a trend toward association with TNM stage (p = 0.02). No significant differences in expression levels of these miRNAs were observed between CRC and PTC samples. Conclusions: Overall, miR-155-5p and miR-221-3p are consistently overexpressed in CRC and PTC, indicating their potential as diagnostic biomarkers. miR-155-5p, in particular, shows promise as a marker of disease progression in CRC. These findings underscore the importance of region-specific studies in advancing our understanding of the molecular landscape of cancer. Full article

Background: Prostate cancer remains a major contributor to cancer-related morbidity and mortality worldwide, emphasizing the need for safer and more effective therapeutic options. Andrographolide, a diterpenoid lactone derived from Andrographis paniculata, has shown promising anticancer activity, yet its effects on microRNA (miRNA) regulation in prostate cancer remain insufficiently explored. Methods: In this study, we evaluated the cytotoxic and molecular effects of andrographolide on two human prostate cancer cell lines, PC3 and LNCaP, along with HEK-293 cells as a noncancerous model. Results: Cell viability assessment using the MTT assay revealed dose-dependent cytotoxicity, with 24 h IC₅₀ values of 82.31 µM for PC3, 68.79 µM for LNCaP, and 133.9 µM for HEK-293 cells. Subsequent expression analysis of key oncogenic and tumor suppressor miRNAs demonstrated that andrographolide induced the upregulation of miR-16-5p, miR-34a-5p, and miR-200a-5p miRNAs implicated in apoptosis, proliferation control, and androgen receptor signaling. In contrast, the expression of oncomiRs miR-21-5p and miR-221-5p showed minimal or nonsignificant changes, reflecting the complex and context-specific roles of miRNAs in prostate cancer. Gene expression profiling further indicated differential transcriptional responses between the two prostate cancer cell lines, consistent with their distinct molecular backgrounds. Conclusions: Although HEK-293 cytotoxicity and previously reported nephrotoxic effects warrant caution, these results support the potential of andrographolide as an adjuvant phytochemical capable of modulating clinically relevant miRNAs in prostate cancer. Future studies investigating optimized delivery systems and validating direct miRNA targets may help advance andrographolide toward safer and more targeted therapeutic applications. Full article

Colorectal cancer (CRC) remains a major cause of cancer-related mortality worldwide. While immune checkpoint blockade (ICB) has transformed cancer therapy, its clinical benefit in CRC is often limited by an immune-excluded tumor microenvironment (TME). MicroRNA-21-5p (miR-21-5p) is a well-established oncomiR in CRC; however, its role in immune resistance remains incompletely elucidated. In this study, we explored the potential immunoregulatory role of miR-21-5p in CRC by integrating transcriptomic profiling of TCGA-COAD and TCGA-READ cohorts with experimental validation of its target PTEN in CRC cell models. MiR-21-5p was markedly upregulated in tumors compared with adjacent normal tissues and was associated with reduced infiltration of CD8⁺ T cells and dendritic cells. Functional assays confirmed that miR-21-5p directly targets PTEN; transcriptomic correlations further suggested potential links to PI3K/AKT activation and alterations in JAK–STAT and Th17-associated signaling. Elevated miR-21-5p was associated with transcriptomic signatures indicative of altered Th1/Th2 balance, reduced IgA-related immune responses, and features of an immune-excluded TME. Therapeutically, the inhibition of miR-21-5p has been reported in previous studies to restore PTEN and modulate signaling pathways. However, our study did not evaluate immune reactivation or checkpoint-blockade efficacy; thus, such therapeutic implications remain hypothetical. Collectively, these findings suggest that the miR-21–PTEN–PI3K/AKT axis may contribute to shaping immune-related features in CRC. These findings provide a rationale for future studies investigating whether targeting miR-21-5p could enhance antitumor immunity or improve immunotherapy response in CRC. Full article

Prostate adenocarcinoma is mainly diagnosed based on serum PSA levels, but elevated PSA levels can also be caused by BPH, which weakens its specificity. Recent scientific studies have demonstrated that specific microRNAs regulate cancer cell proliferation by modulating the Wnt/β-catenin pathway. To date, no published literature has provided a comprehensive assessment of the interactions between miR-106a-5p and miR-375-3p and components of the Wnt/β-catenin pathway in prostate cancer. Therefore, the aim of the present study was to perform a pilot evaluation of the expression of miRNAs 106a-5p and 375-3p, as well as β-catenin, Fzd8, Wnt5a, and cyclin D1 in prostate adenocarcinoma compared with BPH. The study material consisted of samples collected from 30 patients with prostate cancer and 30 with BPH. Protein expression was analyzed using IHC and qRT-PCR methods, while miRNA levels were quantified by dPCR. Our study results revealed lower immunoreactivity and expression of genes encoding β-catenin, Fzd8, Wnt5a, and cyclin D1 and significantly higher fluorescence intensity of miRNA 106a-5p and 375-3p with prostate adenocarcinoma compared to BPH. These parallel alterations in miRNA expression and Wnt/β-catenin-related components reflect disease-specific expression patterns and warrant further investigation in larger cohorts to determine their potential utility as diagnostic biomarkers in prostate diseases. Full article

Metastasis-associated lung adenocarcinoma transcript 1(MALAT1) is associated with vascular calcification and diabetes-related complications. However, the effect of exosomal MALAT1 derived from macrophages induced by hyperglycemia on vascular calcification (VC) remains unclear. In this study, we investigated the effect of VC and its regulatory mechanisms in cultured vascular smooth muscle cells (VSMCs) and diabetic rats by exosomal MALAT1 derived from macrophages treated with high levels of glucose. Macrophages and VSMCs were cultured in 25 mM glucose. Macrophages exposed to high glucose exhibited increased expression of exosomal MALAT1. When transferred to VSMCs, exosomal MALAT1 significantly suppressed the expression of miR-143-3p while upregulating Matrix Gla protein (MGP, an inhibitor of VC) mRNA and protein levels. Interventions using MALAT1 siRNA or miR-143-3p mimics effectively reversed this effect. Both MALAT1 siRNA and overexpression of miR-143-3p significantly increased the calcium content in cultured VSMCs and in the carotid artery of diabetic rats following balloon injury. Balloon injury to the carotid artery in diabetic rats treated with macrophage-derived exosomes significantly increased the expression of MALAT1 and MGP while reducing the expression of miR-143-3p in the carotid artery. These findings demonstrate that macrophage-derived exosomal MALAT1 modulates VC via the MALAT1/miR-143-3p/MGP axis under hyperglycemic conditions. The results suggest that targeting exosomal MALAT1 may offer a novel and effective therapeutic approach for mitigating VC in metabolic disorders such as diabetes. Full article

The “athlete’s heart” phenotype, featuring resting bradycardia, has traditionally been viewed as a benign adaptation. However, emerging evidence associates prolonged, high-intensity endurance training with an increased risk of clinical sinoatrial node dysfunction. This systematic review synthesizes evidence on exercise-induced intrinsic Sinoatrial Node (SAN) electrophysiological remodelling and evaluates its dual nature along the adaptation–pathology continuum. Following PRISMA guidelines, a systematic search of PubMed, Web of Science, and Google Scholar (2000–2025) identified 17 eligible studies. Analysis revealed that in humans, rodents, and rabbits, exercise induces intrinsic SAN electrophysiological remodelling—a “membrane clock” reset characterized by coordinated downregulation of pacemaker currents, notably Hyperpolarization-activated cyclic nucleotide-gated cation channel (I_f), via the Nkx2.5-miR-423-5p transcription factor pathway. Evidence for “calcium clock” involvement remains inconsistent. In contrast, large animal models (e.g., dogs, horses) show only parasympathetic-mediated bradycardia without intrinsic remodelling. Training loads may induce structural changes (e.g., fibrosis), providing an anatomical substrate for pathology. Moderating factors such as training type and ageing contribute to a phenotype of “acquired SAN reserve reduction. Exercise-induced intrinsic SAN remodelling is a physiological adaptation mechanism that, under certain conditions, can cross a threshold to become a pathological cause of clinical dysfunction. Recognizing this continuum is essential for risk stratification and future therapeutic innovation. Full article

Background: Oral squamous cell carcinoma (OSCC) is a highly aggressive neoplasm characterized by grim survival outcomes, despite significant therapeutic advances. Mortality rates (up to 70%) have remained unaltered for decades, predominantly due to profound diagnostic delays. These derive from the asymptomatic nature of the early stages of oral carcinogenesis and the emergence of dysplastic areas in previously benign lesions, acting as the bridge to malignant transformation. Hence, the establishment of reliable salivary biomarkers is crucial for non-invasive OSCC detection, even from the premalignant stage of dysplasia. Based on our previous bioinformatic research identifying stage-specific miRNAs throughout OSCC progression, which yielded miR-34a-5p as the most significant, we aimed to experimentally investigate its role in oral oncogenesis and explore its stage-reflecting biomarker potential for liquid biopsy. Methods: The expression of miR-34a was evaluated using quantitative real-time PCR in saliva samples from 9 patients with oral premalignant dysplastic lesions, 10 patients with OSCC and 10 healthy controls. The diagnostic accuracy of miR-34a expression profiles was assessed using ROC-curve analyses. Results: The expression of salivary miR-34a differed significantly across the studied groups, demonstrating a steep decrease in the presence of epithelial premalignant dysplasia, significant upregulation in OSCC and intermediate levels in normal oral mucosa (p < 0.001). The ROC results indicate strong diagnostic performance for the detection of oral dysplasia (AUC = 0.93; p < 0.001), OSCC (AUC = 0.77; p = 0.01) and excellent accuracy for the discrimination between premalignant and OSCC lesions (AUC = 0.98; p < 0.001). Conclusions: Our findings reveal a state-dependent dysregulation of miR-34a in oral carcinogenesis, suggesting its complex role as a pathogenetic agent that allows for malignant transformation through its diminished expression, and as a secondary reactive mechanism attempting to suppress tumor development. Salivary miR-34a holds great, stage-specific diagnostic potential, thereby reflecting the health state of oral mucosa in real time. Full article

Sympathetic remodeling following myocardial infarction (MI) is a critical mechanism underlying the development of malignant arrhythmias and sudden cardiac death (SCD). The cardiac sympathetic nervous system functions as a multi-level regulatory network, integrating centers from the cerebral cortex (e.g., the insular lobe and anterior cingulate gyrus), subcortical structures (e.g., the paraventricular nucleus of the hypothalamus), and brainstem nuclei (e.g., the rostral ventrolateral medulla and nucleus of the solitary tract), down to the peripheral ganglia. Post-MI, this entire neural axis undergoes significant remodeling, which manifests as neuroinflammation in the central nervous system, alongside peripheral sympathetic nerve sprouting and heterogeneous hyperinnervation. This article provides a systematic review of the anatomical architecture of the cardiac sympathetic nerve and the regulatory mechanisms of sympathetic remodeling at various levels of the central nervous system after MI. It particularly focuses on key signaling pathways—including the TLR4/MyD88/NF-κB and P2X7R/NLRP3 inflammasome pathways, as well as GABAergic inhibition within the paraventricular nucleus—in addition to the peripheral remodeling mechanisms within the stellate ganglia. By synthesizing insights from these studies, this review offers a novel perspective for understanding the neuroimmune mechanisms of post-MI malignant arrhythmias and provides a theoretical foundation for elucidating the mechanisms of SCD in clinical practice. Full article

Long non-coding RNAs (lncRNAs) are known to play regulatory roles in various biological processes, including muscle growth and development. However, their specific roles in the myogenesis of cashmere goats have not been well understood. To address this gap, our study aimed to explore the transcriptomic features of lncRNAs during muscle formation in cashmere goats and identify key lncRNAs involved in this process. We utilized RNA-seq technology to profile lncRNAs at four distinct stages of longissimus dorsi muscle development in cashmere goats: 120 days of fetal age, 1 month, 3 months, and 10 months. Our analysis detected a total of 3480 lncRNAs, including 1141 novel ones. Through a bioinformatics analysis and experimental validation, we focused on a novel lncRNA, designated MSTRG.5182.1, which appears to have significant regulatory functions in cashmere goat myogenesis. We found that downregulating MSTRG.5182.1 inhibits myocyte proliferation and promotes myocyte differentiation. Moreover, knocking down MSTRG.5182.1 affects muscle growth and development by modulating the chi-miR-424-5p/IKBKG signaling pathway. Our study provides an expression profile of lncRNAs during cashmere goat muscle formation and highlights the key role of MSTRG.5182.1 in myogenesis via the chi-miR-424-5p/IKBKG pathway. These findings are crucial for elucidating the molecular regulatory mechanisms underlying muscle development in cashmere goats and hold significant implications for molecular breeding and meat quality improvement in this species. Full article

Exposure to nickel (Ni) and chromium (Cr) in environmental and occupational settings appears to be inevitable and significantly affects the liver, the principal organ responsible for their metabolic processes. This research aimed to assess the functional integrity of the liver and the molecular mechanisms underlying hepatic damage in employees exposed to Ni and Cr at work. A cross-sectional investigation was implemented with 86 non-smoking male employees working in a metallurgical factory. Serum Cr, Ni, liver function tests, oxidative and inflammatory indicators, and Keap-1, Nrf2, and miR-223 expression were assessed. In electroplating workers, serum Cr (2.47 ± 2 µg/L), Ni (1.39 ± 0.79 µg/L), liver transaminases, total bilirubin, and NF-κB were all statistically significantly greater than in the referent group. Electroplaters’ serum albumin levels were significantly lower than those of controls. Furthermore, oxidative stress was observed in electroplaters, characterized by lower levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and greater levels of malondialdehyde (MDA) with respect to controls (p < 0.05). Additionally, compared to controls, gene expressions in electroplaters showed that Keap-1 was upregulated, while Nrf2/Ho-1 and miR-223 were downregulated. In conclusion, occupational exposure to Ni and Cr was associated with hepatic impairment through downregulation of the antioxidant Nrf2 pathway, oxidative stress, and inflammation. Full article

Platelet concentrates (PCs) are used to treat patients with platelet deficiencies. PCs are stored at 20–24 °C under agitation for up to 7 days to maintain platelet functionality, but these conditions are amenable for proliferation of contaminants such as Staphylococcus aureus, posing a risk for transfusion-transmitted infections. We investigated the contribution of staphylococcal enterotoxins (SEs) type G (SEG) and type H (SEH) to platelet activation, cytokine release, microRNA (miRNA) modulation, and in vivo virulence. PCs were inoculated with wildtype S. aureus CBS2016-05 or SE-deficient mutants (Δseg, Δseh, ΔΔsegh) and monitored during storage. Flow cytometry revealed progressive elevation of platelet activation markers CD62P and Annexin V in contaminated PCs, with significantly higher expression in wildtype compared to SE-mutant strains. Cytokine profiling demonstrated that SEs modulate pro- and anti-inflammatory mediators, notably CCL2, TGF-β1, IFN-γ, and TNF-α, implicating SEG in their regulation. Next-generation sequencing and RT-qPCR validation identified transient induction of immune-related microRNAs miR-98-5p, miR-146a-5p, miR-221-3p, miR-320a-3p, with SE-dependent expression patterns. In a silkworm infection model, wildtype S. aureus-contaminated PCs exhibited significantly higher lethality than SE-deficient strains, confirming toxin-mediated virulence. Collectively, these findings reveal that SEs exacerbate platelet activation and immune dysregulation during storage, enhancing bacterial pathogenicity. This study identifies platelet-derived cytokine and miRNA signatures as potential biomarkers of bacterial contamination and underscores the need to mitigate SE-driven platelet dysfunction to improve transfusion safety. Full article