Search Results (8,993)

Background/Objectives: Infertility is a reproductive disorder affecting approximately 10–15% of reproductive-age couples worldwide. Recent studies have suggested that miRNAs in follicular fluid may provide insights into reproductive potential and follicle health. This study evaluated the altered profile of miRNAs in the follicular fluid in patients undergoing IVF, considering the underlying etiology of infertility. Among our study participants, we identified four major underlying causes of infertility: polycystic ovary syndrome (PCOS), pelvic inflammatory disease (PID), male factor infertility, and unexplained infertility (UI). Methods: This study aimed to assess whether these infertility diagnoses are associated with distinct follicular behaviors and to identify altered miRNA patterns linked to these conditions. Ingenuity Pathway Analysis (IPA) was used to evaluate the impact of the altered miRNA signature on key biological processes. Results: The bioinformatics analysis of microarray data revealed altered miRNA patterns in FF for selected subgroups. Compared to healthy controls, 25 differentially expressed miRNAs were identified in PCOS (9 downregulated and 16 overexpressed), 21 in PID (15 downregulated and 6 overexpressed), and 34 in UI (24 downregulated and 10 overexpressed). These altered miRNA signatures indicate a complex interplay with essential signaling pathways, including hormonal regulation and tissue remodeling. Conclusions: Our analysis revealed key miRNAs that were differentially expressed across selected groups, indicating their potential as biomarkers for more accurate diagnosis and targeted treatment strategies. These findings provide valuable insights into the molecular mechanisms underlying reproductive disorders and underscore the importance of further research to develop targeted interventions that can enhance patient outcomes. Full article

Background/Objectives: Competing endogenous RNAs (ceRNA) are molecules that compete for the binding to a microRNA (miR). Usually, there are two ceRNA, one of which is a protein-coding RNA (mRNA), with the other being a long non-coding RNA (lncRNA). The miR role is to inhibit mRNA expression, either promoting its degradation or impairing its translation. The lncRNA can “sponge” the miR, thus impeding its inhibitory action on the mRNA. In their easier configuration, these three molecules constitute a regulatory axis for protein expression. However, each RNA can interact with multiple targets, creating branched and intersected axes that, all together, constitute what is known as a competing endogenous RNA network (ceRNET). Methods: In this systematic review, we collected all available data from PubMed about experimentally verified (by luciferase assay) regulatory axes in endometrial cancer (EC), excluding works not using this test; Results: This search allowed the selection of 172 bibliographic sources, and manually building a series of ceRNETs of variable complexity showed the known axes and the deduced intersections. The main limitation of this search is the highly stringent selection criteria, possibly leading to an underestimation of the complexity of the networks identified. However, this work allows us not only to hypothesize possible gap fillings but also to set the basis to instruct artificial intelligence, using adequate prompts, to expand the EC ceRNET by comparing it with ceRNETs of other cancers. Moreover, these networks can be used to inform and guide research toward specific, though still unidentified, axes in EC, to complete parts of the network that are only partially described, or even to integrate low complexity subnetworks into larger more complex ones. Filling the gaps among the existing EC ceRNET will allow physicians to hypothesize new therapeutic strategies that may either potentiate or substitute existing ones. Conclusions: These ceRNETs allow us to easily visualize long-distance interactions, thus helping to select the best treatment, depending on the molecular profile of each patient, for personalized medicine. This would yield higher efficiency rates and lower toxicity levels, both of which are extremely relevant factors not only for patients’ wellbeing, but also for the legal, regulatory, and ethical aspects of miR-based innovative treatments and personalized medicine as a whole. This systematic review has been registered in PROSPERO (ID: PROSPERO 2025 CRD420251035222). Full article

Background: Lead (Pb), a pervasive environmental toxicant with specific toxicity to bone, has been recognized as a significant etiological factor in the pathogenesis of osteoporosis. While dietary fiber (DF) demonstrates anti-osteoporotic potential, its protective role against Pb-induced bone loss remains unexplored. Methods: This study analyzed the association between dietary fiber, blood lead, and osteoporosis based on the NHANES database, and validated it by constructing a lead exposed mouse model. Micro CT was used to evaluate bone microstructure, ELISA was used to detect bone markers, q-PCR/Western blot was used to measure intestinal tight junction protein, flow cytometry was used to analyze Treg cells in colon/bone tissue, GC-MS was used to detect short chain fatty acids, and 16S rRNA sequencing was used to analyze changes in gut microbiota. The regulatory mechanism of dietary fiber on bone metabolism and intestinal barrier in lead exposed mice was systematically evaluated. Results: Based on NHANES data analysis, it was found that dietary fiber can reduce the risk of osteoporosis in lead exposed populations. Animal experiments have shown that dietary fiber intervention significantly increases bone density, improves bone microstructure and metabolic indicators, repairs intestinal barrier damage caused by lead exposure, and regulates immune balance in lead exposed mice. At the same time, it promotes the generation of short chain fatty acids and the proliferation of beneficial gut microbiota. Conclusions: These findings indicate that DF mitigates Pb-induced osteoporosis through gut barrier restoration, SCFA-mediated immunomodulation, and microbiota-driven Treg cell expansion along the gut–bone axis. Full article

This study aimed to determine the microRNA (miRNA) profile extracted from exosomes in plasma samples in pseudoexfoliation (PEX) glaucoma patients compared to controls. A blood sample (10 mL) was obtained after acquiring written informed consent. Exosome was extracted from each plasma sample using an Exoquick-TC kit. RNA sequencing was performed for each exosome sample. A bioinformatics study was conducted for miRNA-related pathways and targets. A total of 14 Korean subjects (7 with PEX glaucoma; 7 age-matched controls) were involved in the final study. In exosomes of PEX glaucoma participants, 330 mature miRNAs were detected. Among these, three miRNAs were significantly upregulated, including hsa-miR-92b-5p (fold change: 24.68), hsa-miR-744-5p (fold change: 2.49), and hsa-miR-148b-3p (fold change: 3.96). Sixty-six miRNAs were significantly downregulated in PEX glaucoma patients compared to the controls (all p < 0.05). These significantly altered miRNAs (both upregulated and downregulated) were associated with the gene ontology (GO) category of neurogenesis (9.41%), which accounted for the largest proportion. The expression of exosomal microRNAs in plasma was significantly different between PEX glaucoma patients and the controls. This suggests their possible roles in the pathogenic mechanism and a good diagnostic marker for PEX glaucoma. Full article

Rapeseed (Brassica napus) is highly susceptible to waterlogging during the seedling stage; however, most of the studies on its gene expression under waterlogging stress have focused on transcriptional regulation, with little work conducted on post-transcriptional regulation to date. To elucidate this regulatory network, comparative transcriptome and miRNA analyses in the leaves and roots of rapeseed Zhongshuang11 (ZS11) were performed. Differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) were identified by comparing the normal planting condition (the control group, CKT) with waterlogging treatment (WLT). DEGs identified in leaves and roots were enriched in different metabolic pathways, indicating their distinct mechanisms in response to waterlogging stress. In total, 68 and 82 DEmiRNAs were identified in leaves and roots, respectively, predicted to target 543 and 2122 DEGs in each tissue. Among these, 12 and 9 transcription factors (TFs) were exclusively targeted by DEmiRNAs in leaves and roots, respectively. Notably, six upregulated TFs in leaves were associated with the ethylene response and were predicted targets of bna-miR172 family members, and four TFs in roots participated in the ethylene response pathway. Furthermore, bna-miR169, along with novel-miR-23108 and novel-miR-42624 family members, played crucial roles in waterlogging response of rapeseed. Combining with the determination results of ethylene and jasmonic acid content, a preliminary model of miRNA-mediated gene expression regulation in rapeseed response to waterlogging stress was developed. These findings advance our understanding of transcriptional regulation under waterlogging and lay a theoretical foundation for improving rapeseed waterlogging tolerance. Full article

Background: Single-nucleotide polymorphisms (SNPs) are associated with multiple disorders and various cancer types. In the context of cancer, alterations within non-coding regions, specifically 3′ untranslated regions (3′ UTR), have proven substantially important. Methods: In this study, we utilized various bioinformatics tools to examine the effect of SNPs in the 3′ UTR. We retrieved the 3′ UTR SNPs of the Signal Transducer and Activator of Transcription 1 (STAT1) gene from the National Centre for Biotechnology Information (NCBI) website. Next, we employed the Polymorphism in miRNAs and their corresponding target sites (PolymiRTS) database to predict the 3′ UTR SNPs that create new microRNA (miRNA) binding sites and their respective miRNAs. The effect of the 3′ UTR SNPs on the messenger RNA structure was studied using RNAfold server. We used Cscape tool to predict the oncogenic 3′ UTR SNPs. Then, we submitted the miRNAs to the miRNet database to visualize the miRNA-miRNAs’ target genes interaction, for which gene enrichment analysis was performed using ShinyGO. Protein–protein interactions were conducted using the STRING database. We conducted miRNA enrichment analysis utilizing miRPathDB, subsequently performing miRNA differential expression analysis through oncoMIR, and the StarBase database. The survival analysis of the upregulated miRNAs in cancer was investigated using the Kaplan–Meier Plotter. Result: Twelve SNPs were predicted to create new miRNA binding sites. Two of them, rs188557905 and rs190542524, were predicted to destabilize the mRNA structures. We predicted rs190542524, rs11305, rs186033487, and rs188557905 to be oncogenic 3′ UTR SNPs, with high-confidence predictions and scores > 0.5. Using miRNAs’ target genes enrichment analysis, this study indicated that the miRNA target genes were more likely to be involved in cancer-related pathways. Our comprehensive analysis of miRNAs, their functional enrichment, their expression in various types of cancer, and the correlation between miRNA expression and survival outcome yielded these results. Our research shows that the oncogenic 3′ UTR SNP rs190542524 creates a new binding site for the oncogenic miRNA hsa-miR-136-5p. This miRNA is significantly upregulated in BLCA, LUSC, and STAD and is linked to poor survival. Additionally, rs114360225 creates a new binding site for hsa-miR-362-3p, influencing LIHC. Conclusions: These analyses suggest that these 3′ UTR SNPs may have a functional impact on the STAT1 gene’s regulation through their predicted effect on miRNA binding sites. Future experimental validation could establish their potential role in the diagnosis and treatment of various diseases, including cancer. Full article

Adipocyte differentiation is a complex process in which pluripotent mesenchymal stem cells (MSCs) differentiate and develop into mature fat cells, also known as adipocytes. This process is controlled by various transcription factors, hormones, and signaling molecules that regulate the development of these cells. Recently, an increasing number of non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), have been established to be involved in the regulation of many biological processes, including adipocyte differentiation, development, metabolism, and energy homeostasis of white and brown adipose tissue. Several in vitro and in vivo studies reported the significant role of ncRNAs in either promoting or inhibiting adipocyte differentiation into white or brown fat cells by targeting specific transcription factors and regulating the expression of key adipogenic genes. Identifying the function of ncRNAs and their subsequent targets contributes to our understanding of how these molecules can be used as potential biomarkers and tools for therapies against obesity, diabetes, and other diseases related to obesity. This could also contribute to advancements in tissue-engineering based treatments. In this review, we intended to present an up-to-date comprehensive literature overview of the role of ncRNAs, including miRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), focusing particularly on miRNAs, in regulating the differentiation and development of cells into white and brown adipose tissue. In addition, we further discuss the potential use of these molecules as biomarkers for the development of novel therapeutic strategies for future personalized treatment options for patients. Full article

In this study, we address the role of c-ABL (cellular Abelson Tyr kinase) in the cytoskeletal rearrangements induced by DENV (Dengue virus) infection in mammalian cells. Using the specific inhibitor imatinib and targeted RNA interference, we show that c-ABL is necessary for viral entry and subsequent ENV (DENV envelope protein) accumulation in infected cells. In addition, c-ABL targeting attenuates F-actin reorganization induced by DENV infection. Together with the involvement of c-ABL in endothelial dysfunction induced by DENV and host secreted factors, our findings strongly suggest that c-ABL is a potential host-targeted antiviral that could control DENV infection and/or its evolution to more severe forms of the disease. Full article

Peptide nucleic acids (PNAs) are synthetic analogues of DNA/RNA characterized by the absence of negative phosphate groups, which confer a low sensitivity to ionic strength for hybridization with respect to the canonical counterpart. PNAs are a suitable probe for miRNAs, as well as endogenous molecules of single-strand non-coding RNA whose dysregulation is often linked to several diseases. The interaction forces between PNA and microRNA-155 (miR-155), a multifunctional microRNA overexpressed in a variety of tumors, were investigated by Atomic Force Spectroscopy (AFS) in fluid under different conditions. We found that the unbinding forces acquired at the ionic strength of 150 mM for a rather wide range of loading rates (ΔF/Δt) can be described using the Bell–Evans model. This allows us to extract information on the kinetics and thermodynamic properties of the miR-155/PNA duplex. Additionally, we probed the unbinding forces and the target recognition times between miR-155 and PNA in the 50–300 mM ionic strength range. Our results indicate that both of these parameters are practically independent from the ionic strength in the analyzed range. The results provide information that is useful for a wider use of PNA in biosensors for diagnostics and therapeutics, even in situ. Full article

Resistance to tyrosine kinase inhibitors (TKIs, e.g., sorafenib and lenvatinib) presents a significant hurdle for hepatocellular carcinoma (HCC) treatment, underscoring the need to decipher the underlying mechanisms for improved therapeutic strategies. MicroRNAs (miRNAs) have emerged as critical modulators in HCC progression and TKI resistance. In this study, we report a positive correlation between the expression levels of a tumor suppressor miRNA, miR-142-3p, and increased sensitivity to sorafenib and lenvatinib, supported by clinical data from the BIOSTORM HCC cohort. Overexpression of miR-142-3p in TKI-resistant HCC cells significantly inhibited proliferation and colony formation, induced apoptosis, increased cell cycle arrest at the G2 phase, and reduced migration and invasion by reversing epithelial–mesenchymal transition. Notably, combining miR-142-3p with lenvatinib synergistically inhibited growth in both inherent and acquired TKI-resistant HCC cells by modulating critical signaling pathways, including STAT3, PI3K/AKT, MAPK, YAP1, and by impeding autophagic influx. RNA-sequencing of a TKI-resistant HCC cell line ± miR-142-3p overexpression identified YES1 and TWF1 as direct downstream target genes of miR-142-3p, both of which are key genes associated with drug resistance in HCC. Small interfering RNA (siRNA)-mediated knockdown of these genes mirrored the antitumor effects of miR-142-3p and enhanced TKI sensitivity, with YES1 knockdown decreasing YAP1 phosphorylation, and TWF1 knockdown inhibiting autophagy. Collectively, these findings indicate that restoring miR-142-3p expression or targeting its downstream effectors YES1 and TWF1 offers a promising strategy to overcome drug resistance and improve therapeutic outcome in HCC. Full article

Colorectal cancer remains one of the leading causes of cancer-related deaths globally. Non-protein coding RNAs, including microRNAs, have emerged as crucial regulators in cancer progression. Herein, we analyzed publicly available datasets for miRNA expression in healthy controls, adenomatous polyps, and colorectal cancer and identified their regulatory networks using HCT116 and HT-29 CRC models. Differentially expressed miRNAs in adenomatous polyps and colorectal cancer were identified, highlighting their role in colorectal cancer initiation and progression. Notably, miR-218-5p was significantly downregulated in adenomatous polyps and colorectal cancer, suggesting a role in colorectal cancer initiation. Functional investigations revealed a tumor suppressive role for miR-218-5p in HCT116 and HT-29 CRC cell models, affecting cell proliferation and three-dimensional organoid formation and promoting cell death. RNA-Seq and bioinformatics identified BIRC5 and DDX21 as bona fide gene targets for miR-218-5p, validated by reverse transcription quantitative PCR and Western blotting. Further investigation into the genomic location of miR-218-5p, embedded within the SLIT2 and SLIT3 introns on chromosome 4 and chromosome 5, respectively, revealed epigenetic silencing through promoter hypermethylation in colorectal cancer cell models. These findings highlight epigenetic silencing of miR-218-5p in colorectal cancer, suggesting its potential as a biomarker and therapeutic target for early detection and intervention. Full article

Aedes aegypti is a major vector of arboviruses, including dengue, Zika, chikungunya, yellow fever, and Mayaro. The extensive use of insecticides has led to resistance, complicating vector control efforts. MicroRNAs (miRNAs) are post-transcriptional regulators involved in detoxification and stress adaptation; however, their role in the insecticide response of Ae. aegypti remains unclear. This study analyzed miRNA expression in Ae. aegypti following imidacloprid exposure, comparing a field strain, Martinez de la Torre from Mexico (MT), and a susceptible reference strain, New Orleans (NO). Small RNA sequencing identified 96 miRNAs, with miR-1, miR-281-5p, miR-100, and miR-184 being consistently expressed across all conditions. In contrast, let-7, miR-124, and miR-13-3p were exclusively detected in wild mosquitoes exposed to imidacloprid, while miR-14 and miR-275-3p showed condition-specific expression. Distinct miRNA expression patterns were observed between the field and susceptible strains, with specific miRNAs showing condition-dependent expression. These findings suggest that certain miRNAs may serve as potential biomarkers for resistance monitoring, contributing to a better understanding of insecticide response mechanisms and informing novel vector control strategies. Full article

Carbohydrate metabolism disorders (CMDs), including prediabetes and type 2 diabetes mellitus (T2DM), are increasingly prevalent in the aging population. Oxidative stress (OxS) plays a pivotal role in CMD pathogenesis, with extracellular superoxide dismutase (SOD3) and catalase (CAT) serving as critical antioxidant defenses. Additionally, microRNAs (miR-21 and miR-30b) regulate the oxidative and inflammatory pathways, yet their roles in elderly CMD patients remain unclear. This study evaluated miR-21 and miR-30b expression alongside SOD3 and CAT plasma levels in individuals aged ≥ 65 years (n = 126) categorized into control (n = 38), prediabetes (n = 37), and T2DM (n = 51) groups. Quantitative PCR assessed miRNA expression, while ELISA measured the enzyme levels. SOD3 levels were significantly reduced in CMDs, particularly in T2DM, whereas miR-21 was upregulated. A negative correlation between SOD3 and miR-21 was strongest in T2DM, suggesting a regulatory interplay. Neither CAT levels nor miR-30b expression differed among groups. Logistic regression indicated SOD3 as a protective biomarker, with each 1 ng/mL increase reducing the CMD risk by ~5–6%. The ROC analysis supported SOD3’s diagnostic potential, while miR-21 showed a modest association. These findings highlight SOD3 downregulation and miR-21 upregulation as potential contributors to CMD progression in elderly patients, warranting further research into their mechanistic roles and therapeutic potential. Full article

(1) Background: Circular RNAs (circRNAs) are covalently closed single-stranded molecules that play crucial roles in gene regulation, while microRNAs (miRNAs), specifically mature microRNAs, are naturally occurring small molecules of non-coding RNA with 17-25-nucleotide sizes. Understanding circRNA–miRNA interactions (CMIs) can reveal new approaches for diagnosing and treating complex human diseases. (2) Methods: In this paper, we propose a novel approach for predicting CMIs based on a graph attention network (GAT). We utilized DNABERT to extract molecular features of the circRNA and miRNA sequences and role-based graph embeddings generated by Role2Vec to extract the CMI features. The GAT’s ability to learn complex node dependencies in biological networks provided enhanced performance over the existing methods and the traditional deep neural network models. (3) Results: Our simulation studies showed that our GAT model achieved accuracies of 0.8762 and 0.8837 on the CMI-9905 and CMI-9589, respectively. These accuracies were the highest among the other existing CMI prediction methods. Our GAT method also achieved the highest performance as measured by the precision, recall, F1-score, area under the receiver operating characteristic (AUROC) curve, and area under the precision–recall curve (AUPR). (4) Conclusions: These results reflect the GAT’s ability to capture the intricate relationships between circRNAs and miRNAs, thus offering an efficient computational approach for prioritizing potential interactions for experimental validation. Full article

Renal cell carcinoma (RCC) presents a significant diagnostic challenge, particularly in small renal masses. The search for non-invasive screening methods and biomarkers has directed research toward liquid biopsy, which focuses on microRNAs (miRNAs), exosomes, and circulating tumor cells (CTCs). miRNAs are small non-coding RNA molecules that show considerable dysregulation in RCC, and they have potential for both diagnostic and prognostic applications. Research has highlighted their utility on biofluids, such as plasma, serum, and urine, in detecting RCC and characterizing its subtypes. Promising miRNA signatures have been associated with overall survival, suggesting their potential importance in the management of RCC. Exosomes, which carry a variety of molecular components, including miRNAs, are emerging as valuable biomarkers, whereas CTCs, released from primary tumors into the bloodstream, provide critical information on cancer progression. However, translation of these findings into clinical practice requires additional validation and standardization through large-scale studies and robust evidence. Although there are currently no approved diagnostic tests for RCC, the future potential of liquid biopsy in monitoring, treatment decision-making, and outcome prediction in patients with this disease is significant. This review examined and discussed recent developments in liquid biopsy for RCC, assessing both the strengths and limitations of these approaches for managing this disease. Full article