microRNA Interactions Research Articles

Profiles and interactions of gut microbiome and intestinal microRNAs in pediatric Crohn's disease.

Since previous studies have focused on the change of the fecal gut microbiome and intestinal tissue miRNA in pediatric Crohn's disease (CD), the relationship between them in different stages is still not clear. This is the first study to explore the gut microbiota and miRNA and their correlations with the Pediatric Crohn's Disease Activity Index (PCDAI). Crohn's Disease Endoscopic Index of Severity (CDEIS), and calprotectin, by applying two omics approach in three different groups (active CD, CD in remission with exclusive enteral nutrition or infliximab induction therapy, and the healthy controls). Both gut microbiome structure and the miRNA profiles were significantly changed in the different stage of CD. Seven key gut microbiome at species and eight key miRNAs were found, and their close interactions were further fully investigated by miRNA target prediction.

The Use of Identified Hypoxia-related Genes to Generate Models for Predicting the Prognosis of Cerebral Ischemia‒reperfusion Injury and Developing Treatment Strategies.

Cerebral ischemia‒reperfusion injury (CIRI) is a type of secondary brain damage caused by reperfusion after ischemic stroke due to vascular obstruction. In this study, a CIRI diagnostic model was established by identifying hypoxia-related differentially expressed genes (HRDEGs) in patients with CIRI. The ischemia‒reperfusion injury (IRI)-related datasets were downloaded from the Gene Expression Omnibus (GEO) database ( http://www.ncbi.nlm.nih.gov/geo ), and hypoxia-related genes in the Gene Cards database were identified. After the datasets were combined, hypoxia-related differentially expressed genes (HRDEGs) expressed in CIRI patients were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the HRDEGs were performed using online tools. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed with the combined gene dataset. CIRI diagnostic models based on HRDEGs were constructed via least absolute shrinkage and selection operator (LASSO) regression analysis and a support vector machine (SVM) algorithm. The efficacy of the 9 identified hub genes for CIRI diagnosis was evaluated via mRNA‒microRNA (miRNA) interaction, mRNA-RNA-binding protein (RBP) network interaction, immune cell infiltration, and receiver operating characteristic (ROC) curve analyses. We then performed logistic regression analysis and constructed logistic regression models based on the expression of the 9 HRDEGs. We next established a nomogram and calibrated the prediction data. Finally, the clinical utility of the constructed logistic regression model was evaluated via decision curve analysis (DCA). This study revealed 9 critical genes with high diagnostic value, offering new insights into the diagnosis and selection of therapeutic targets for patients with CIRI. : Not applicable.

BEROLECMI: a novel prediction method to infer circRNA-miRNA interaction from the role definition of molecular attributes and biological networks

Circular RNA (CircRNA)–microRNA (miRNA) interaction (CMI) is an important model for the regulation of biological processes by non-coding RNA (ncRNA), which provides a new perspective for the study of human complex diseases. However, the existing CMI prediction models mainly rely on the nearest neighbor structure in the biological network, ignoring the molecular network topology, so it is difficult to improve the prediction performance. In this paper, we proposed a new CMI prediction method, BEROLECMI, which uses molecular sequence attributes, molecular self-similarity, and biological network topology to define the specific role feature representation for molecules to infer the new CMI. BEROLECMI effectively makes up for the lack of network topology in the CMI prediction model and achieves the highest prediction performance in three commonly used data sets. In the case study, 14 of the 15 pairs of unknown CMIs were correctly predicted.

Interaction of Exosomal MicroRNA and Oxidative Stress in the Pathogenesis of Colitis-Associated Cancer.

Colitis-associated cancer (CAC) is the most serious complication of inflammatory bowel disease. In recent years, the incidence of CAC has increased worldwide. Oxidative stress (OS) is involved in the development of CAC through oxidative damage to biomolecules or activation of inflammatory signaling pathways. Exosomes are extracellular vesicles that act as messengers to deliver signals and macromolecules to target cells, making them important mediators of intercellular communication and exchange of biologically active molecules between cells. MicroRNAs (miRNAs) carried by exosomes regulate the pro- and anti-inflammatory pathways of OS and play a key role in communication between OS and cancer cells. This review describes the correlation between OS and exosomal miRNAs with the goal of identifying a novel therapeutic method for CAC.

Selenium biomarkers and miR‐7‐5p in overweight/obese women

IntroductionChronic low-grade inflammation and oxidative stress are pivotal contributors to the metabolic complications associated with obesity. Selenoprotein P (SELENOP) and glutathione peroxidase 1 (GPx1) are selenoproteins involved in the reduction of reactive oxygen species and pro-inflammatory cytokines levels. Nutritional epigenomics revealed the interaction of microRNAs and nutrients with an important impact on metabolic pathways involved in obesity. However, the knowledge regarding the influence of microRNA on selenium biomarkers and its impact on metabolic pathways related to obesity remains scarce. Thus, the aim of this study was to investigate the association of plasma miR‐7‐5p expression with selenium and inflammatory biomarkers in women with overweight/obesity. Material and methodsAnthropometric evaluations were performed and blood samples were collected for the analysis of fasting glucose, insulin, inflammatory and selenium biomarkers, and miR-7–5p expression in 54 women with overweight/obesity. Gene expression of SELENOP and GPX1 were evaluated in peripheral mononuclear blood cells. ResultsThis study observed a negative correlation between SELENOP levels and miR-7–5p (rho = −0.350; p = 0.018). Additionally, it was observed that body fat (OR = 0.737; p = 0.011), age (OR = 1.214; p = 0.007), and miR‐7‐5p (OR = 0.990; p = 0.015) emerged as significant predictors of SELENOP levels. ConclusionsIn conclusion, we observed a significant inverse association between miR‐7‐5p expression and SELENOP concentration in overweight/obese women, suggesting that age and percentage of body fat are also associated. Trial registration numberBrazilian Registry of Clinical Trials (ReBEC) number RBR-2nfy5q

Roles of long non‑coding RNAs in esophageal cell squamous carcinoma (Review).

Esophageal squamous cell carcinoma (ESCC) is a prevalent and deadly malignancy of the digestive tract. Recent research has identified long non‑coding RNAs (lncRNAs) as crucial regulators in the pathogenesis of ESCC. These lncRNAs, typically exceeding 200 nucleotides, modulate gene expression through various mechanisms, including the competing endogenous RNA (ceRNA) pathway and RNA‑protein interactions. The current study reviews the multifaceted roles of lncRNAs in ESCC, highlighting their involvement in processes such as proliferation, migration, invasion, epithelial‑mesenchymal transition, cell cycle progression, resistance to radiotherapy and chemotherapy, glycolysis, apoptosis, angiogenesis, autophagy, tumor growth, metastasis and the maintenance of cancer stem cells. Specific lncRNAs like HLA complex P5, LINC00963 and non‑coding repressor of NFAT have been shown to enhance resistance to radio‑ and chemotherapy by modulating pathways such as AKT signaling and microRNA interaction, which promote cell survival and proliferation under therapeutic stress. Furthermore, lncRNAs like family with sequence similarity 83, member A antisense RNA 1, zinc finger NFX1‑type containing 1 antisense RNA 1 and taurine upregulated gene 1 are implicated in enhancing invasive and proliferative capabilities of ESCC cells through the ceRNA mechanism, while interactions with RNA‑binding proteins further influence cancer cell behavior. The comprehensive analysis underscores the potential of lncRNAs as biomarkers for prognosis and therapeutic targets in ESCC, suggesting avenues for future research focused on elucidating the detailed molecular mechanisms and clinical applications of lncRNAs in ESCC management.

Variances in the Expression Profile of Circadian Clock-Related Genes in Astrocytic Brain Tumors.

This study explores the role of circadian clock genes in the progression of astrocytic tumors, a prevalent type of brain tumor. The aim was to assess the expression patterns of these genes in relation to the tumor grade. Using microarray analysis, qRT-PCR, and methylation-specific PCR, we examined gene expression, DNA methylation patterns, and microRNA interactions in tumor samples from 60 patients. Our results indicate that the expression of key circadian clock genes, such as clock circadian regulator (CLOCK), protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2), protein kinase AMP-activated non-catalytic subunit beta 1 (PRKAB1), protein kinase AMP-activated non-catalytic subunit beta 2 (PRKAB2), period circadian regulator 1 (PER1), period circadian regulator 2 (PER2) and period circadian regulator 3 (PER3), varies significantly with the tumor grade. Notably, increased CLOCK gene expression and protein levels were observed in higher-grade tumors. DNA methylation analysis revealed that the promoter regions of PER1-3 genes were consistently methylated, suggesting a mechanism for their reduced expression. Our findings also underscore the complex regulatory mechanisms involving miRNAs, such as hsa-miR-106-5p, hsa-miR-20b-5p, and hsa-miR-30d-3p, which impact the expression of circadian clock-related genes. This underscores the importance of circadian clock genes in astrocytic tumor progression and highlights their potential as biomarkers and therapeutic targets. Further research is needed to validate these results and explore their clinical implications.

Maintenance of steady-state mRNA levels by a microRNA-based feed forward loop in the presence of stochastic gene expression noise

Abstract All vital functions of living cells rely on the production of various functional molecules through gene expression. The production periods are burst-like and stochastic due to the discrete nature of biochemical reactions. In certain contexts, the concentrations of RNA or protein require regulation to maintain a fine internal balance within the cell. Here we consider a motif of two types of RNA molecules – mRNA and an antagonistic microRNA – which are encoded by a shared coding sequence and form a feed forward loop (FFL). This control mechanism is shown to be perfectly adapting in the deterministic context. We demonstrate that the adaptation (of the mean value) becomes imperfect if production occurs in random bursts. The FFL nevertheless outperforms the benchmark feedback loop in terms of counterbalancing variations in the signal. Methodologically, we adapt a hybrid stochastic model, which has widely been used to model a single regulatory molecule, to the current case of a motif involving two species; the use of the Laplace transform thereby circumvents the problem of moment closure that arises owing to the mRNA–microRNA interaction. We expect that the approach can be applicable to other systems with nonlinear kinetics.

Functional Analysis of BRCA1 3'UTR Variants Predisposing to Breast Cancer.

Breast Cancer (BC) is the main female cancer diagnosed worldwide, and it has been described that few genes, such as BRCA1, have a high penetrance for this type of cancer. In this manuscript, we were interested in evaluating the effect of 3'UTR variants on BRCA1 expression. To accomplish this objective, Whole Exome Sequencing (WES) data of 400 patients with unselected BC was used to filter variants located in the region of interest of BRCA1 gene, finding two of them (c.*36C>G and c.*369_373del). miRGate and miRanda in silico tools were used to predict microRNA (miRNA) interaction. The two variants (c.*36C>G, c.*369_373del) were predicted to affect miRNA interaction. After cloning of BRCA1 3'UTR into pMIR-Report vector, the construct was transfected into two BC cell lines (MDA-MB-231 and MCF-7), and the variant c.*36C>G evidenced overexpression of reporter gene luciferase, showing that the transcript was not being degraded by the miRNA in MDA-MB-231 cells. The variant seems to protect against Triple Negative BC probably due to the expression level of miRNA in this particular cell line (MDA-MB-231). This is consistent with the clinical history of the patients who harbor BC Hormone Receptors positive (HR+).

Dynamics of a diffusive model for cancer stem cells with time delay in microRNA-differentiated cancer cell interactions and radiotherapy effects

Understand the dynamics of cancer stem cells (CSCs), prevent the non-recurrence of cancers and develop therapeutic strategies to destroy both cancer cells and CSCs remain a challenge topic. In this paper, we study both analytically and numerically the dynamics of CSCs under radiotherapy effects. The dynamical model takes into account the diffusion of cells, the de-differentiation (or plasticity) mechanism of differentiated cancer cells (DCs) and the time delay on the interaction between microRNAs molecules (microRNAs) with DCs. The stability of the model system is studied by using a Hopf bifurcation analysis. We mainly investigate on the critical time delay τc\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ au _{c}$$\\end{document}, that represents the time for DCs to transform into CSCs after the interaction of microRNAs with DCs. Using the system parameters, we calculate the value of τc\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ au _{c}$$\\end{document} for prostate, lung and breast cancers. To confirm the analytical predictions, the numerical simulations are performed and show the formation of spatiotemporal circular patterns. Such patterns have been found as promising diagnostic and therapeutic value in management of cancer and various diseases. The radiotherapy is applied in the particular case of prostate model. We calculate the optimum dose of radiation and determine the probability of avoiding local cancer recurrence after radiotherapy treatment. We find numerically a complete eradication of patterns when the radiotherapy is applied before a time t<τc\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$t < \ au _{c}$$\\end{document}. This scenario induces microRNAs to act as suppressors as experimentally observed in prostate cancer. The results obtained in this paper will provide a better concept for the clinicians and oncologists to understand the complex dynamics of CSCs and to design more efficacious therapeutic strategies to prevent the non-recurrence of cancers.

Interaction of Long Non-Coding RNAs and MicroRNAs on Human Papillomavirus and Epstein–Barr Virus-Associated Cancers: A Narrative Review

Interaction of Long Non-Coding RNAs and MicroRNAs on Human Papillomavirus and Epstein–Barr Virus-Associated Cancers: A Narrative Review

Identification of potential regulatory mechanisms and therapeutic targets for lung cancer

Lung cancer poses a significant health threat globally, especially in regions like India, with 5-year survival rates remain alarmingly low. Our study aimed to uncover key markers for effective treatment and early detection. We identified specific genes related to lung cancer using the BioXpress database and delved into their roles through DAVID enrichment analysis. By employing network theory, we explored the intricate interactions within lung cancer networks, identifying ASPM and MKI67 as crucial regulator genes. Predictions of microRNA and transcription factor interactions provided additional insights. Examining gene expression patterns using GEPIA and KM Plotter revealed the clinical relevance of these key genes. In our pursuit of targeted therapies, Drug Bank pointed to methotrexate as a potential drug for the identified key regulator genes. Confirming this, molecular docking studies through Swiss Dock showed promising binding interactions. To ensure stability, we conducted molecular dynamics simulations using the AMBER 16 suite. In summary, our study pinpoints ASPM and MKI67 as vital regulators in lung cancer networks. The identification of hub genes and functional pathways enhances our understanding of molecular processes, offering potential therapeutic targets. Importantly, methotrexate emerged as a promising drug candidate, supported by robust docking and simulation studies. These findings lay a solid foundation for further experimental validations and hold promise for advancing personalized therapeutic strategies in lung cancer. Communicated by Ramaswamy H. Sarma

What is the role of circRNAs in the pathogenesis of cervical cancer? A systematic literature review.

Cervical Cancer (CC) is one of the most prevalent neoplasms among women, considered the leading cause of gynecological death worldwide, and the fourth most common type of cancer. Regional metastasis is closely related to the low effectiveness of treatment, and validating biomarkers can optimize accuracy in diagnosis and prognosis. Among the potential biomarkers associated with disease metastasis are circular RNAs (circRNAs), whose altered expression has been linked to CC progression. In this context, this systematic review aims to compile information on the clinical-pathological significance and describe the biological function of circRNAs. Inclusion and exclusion criteria were used to include relevant literature, followed by in silico analysis. Additionally, we employed the UALCAN tools to search for host genes of circRNAs and expression data, miRTargetLink 2.0 to predict interactions of microRNA target genes and the Cytoscape software to predict possible interactions of microRNA target genes. According to the research, most circRNAs were found to be overexpressed and described as regulators of processes such as invasion, cell proliferation, apoptosis and migration. They were also implicated in clinical significance, including metastasis, TNM staging and microRNA interactions. CircRNAs may participate in critical processes in tumorigenesis; therefore, understanding the underlying molecular mechanisms of gene regulation in CC can contribute to the accuracy of diagnosis, prognosis and therapy.

Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects.

Recent scientific investigations have revealed the intricate mechanisms underlying bone formation, emphasizing the essential role of long non-coding RNAs (lncRNAs) as critical regulators. This process, essential for skeletal strength and functionality, involves the transformation of mesenchymal stem cells into osteoblasts and subsequent deposition of bone matrix. lncRNAs, including HOX transcript antisense RNA (HOTAIR), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), differentiation antagonizing non-coding RNA (DANCR), and maternally expressed gene 3 (MEG3), have emerged as prominent players in this regulatory network. HOTAIR modulates osteoblast differentiation by interacting with chromatin-modifying enzymes, while MALAT1 regulates osteogenic differentiation through microRNA interactions. DANCR collaborates with Runx2 to fine-tune osteoblast differentiation, and MEG3 orchestrates multiple signaling pathways crucial for bone formation. Moreover, other lncRNAs such as H19, lncRNA for enhancing osteogenesis 3, rhabdomyosarcoma 2-associated transcript, urothelial cancer associated 1, taurine up-regulated gene 1, and nuclear enriched abundant transcript 1 contribute to the complex regulatory network governing osteoblast activities. Understanding the precise roles of these lncRNAs offers promising avenues for developing innovative therapeutic strategies targeting bone-related disorders like osteoporosis. Overall, this review summarizes the pivotal role of lncRNAs in bone formation, highlighting their potential as targets for future research endeavors aimed at advancing therapeutic interventions in bone diseases.

Prediction of microRNA target genes for diagnosis and prognosis of asthma development

Given the intricacy of diagnosis, there's an urgent necessity to establish objective and quantifiable biological indicators to enhance the accuracy of diagnosing asthma in its early stages. MicroRNAs emerge as promising candidates for asthma diagnosis. By leveraging the correlations between established target genes and microRNAs, a methodology for early asthma diagnosis can be formulated. A comprehensive database containing microRNAs and target genes implicated in asthma development has been compiled. The dynamics of microRNA interaction with target genes crucial for diagnosing and predicting the progression of asthma have been investigated. Specific microRNA binding sites with target genes involved in asthma development have been pinpointed. Using the DIANA-microTCDS program, features of microRNA interaction with target genes linked to asthma development have been analyzed. Notably, binding sites with significant occurrences have been identified in genes such as IL13, VEGFA, ADRB2, ALDH2, IL10, and DPP10. The conservativity of microRNA binding sites to mRNA genes has been demonstrated.

Establishing mRNA and microRNA interactions driving disease heterogeneity in amyotrophic lateral sclerosis patient survival.

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease, associated with the degeneration of both upper and lower motor neurons of the motor cortex, brainstem and spinal cord. Death in most patients results from respiratory failure within 3-4 years from symptom onset. However, due to disease heterogeneity some individuals survive only months from symptom onset while others live for several years. Identifying specific biomarkers that aid in establishing disease prognosis, particularly in terms of predicting disease progression, will help our understanding of amyotrophic lateral sclerosis pathophysiology and could be used to monitor a patient's response to drugs and therapeutic agents. Transcriptomic profiling technologies are continually evolving, enabling us to identify key gene changes in biological processes associated with disease. MicroRNAs are small non-coding RNAs typically associated with regulating gene expression, by degrading mRNA or reducing levels of gene expression. Being able to associate gene expression changes with corresponding microRNA changes would help to distinguish a more complex biomarker signature enabling us to address key challenges associated with complex diseases such as amyotrophic lateral sclerosis. The present study aimed to investigate the transcriptomic profile (mRNA and microRNA) of lymphoblastoid cell lines from amyotrophic lateral sclerosis patients to identify key signatures that are distinguishable in those patients who suffered a short disease duration (<12 months) (n = 22) compared with those that had a longer disease duration (>6 years) (n = 20). Transcriptional profiling of microRNA-mRNA interactions from lymphoblastoid cell lines in amyotrophic lateral sclerosis patients revealed differential expression of genes involved in cell cycle, DNA damage and RNA processing in patients with longer survival from disease onset compared with those with short survival. Understanding these particular microRNA-mRNA interactions and the pathways in which they are involved may help to distinguish potential therapeutic targets that could exert neuroprotective effects to prolong the life expectancy of amyotrophic lateral sclerosis patients.

In-silico identification and characterization of sucrose transporter genes and their differential expression pattern under salinity stress in Glycine max

Plant sucrose transporters, involved in sugar transport, are key in facilitating sugar flux across the plant cell membranes. However, external stress stimuli significantly impact these sucrose transporters (SWEET/MST/SUT) and, ultimately, the distribution of photosynthates. This has importance as sucrose is a prime energy source, a signaling molecule, and an osmolyte playing a key role in growth and development processes. This study aims to identify and comprehensive in silico characterization and involvement of soybean sucrose transporters GlymaSWEET, GlymaMST, and GlymaSUT in plant development and salt stress responses in an important oilseed crop soybean (Glycine max L.). A genome-wide screening of soybean revealed 13 GlymaSWEET, 6 GlymaMST, and 5 GlymaSUT orthologues as confirmed from the eggNOG database. Probable sites of these proteins were found to be the membranes of cells and organelles, as suggested by their sub-cellular localization. The cis-regulatory elements of these transporters’ promoters indicated their involvement in environmental stress responses. MicroRNA interactions with these transporters were also studied, besides 3-D protein structure prediction using in silico approaches. To gain an insight into the functional divergence of GlymaSWEET, GlymaMST, and GlymaSUT transporters, qRT-PCR-based gene expression analysis was done both in control and salt-treated root and leaf tissues of two contrasting Indian soybean varieties MAUS-47 (salt-tolerant) and Gujosoya-2 (salt-sensitive). Differential gene expression was observed with varying degrees amongst the varieties and the treatments. Overall, we can conclude that the identified GlymaSWEET, GlymaMST, and GlymaSUT have the potential to be explored as candidate genes for engineering salinity stress tolerance in soybean and other plants.

MicroRNA-217-5p triggers dopaminergic neuronal degeneration via autophagy activation under Atrazine exposure

Atrazine (ATR) is a widely used agricultural herbicide, and its accumulation in soil and water can cause various environmental health problems. ATR has neurotoxic effects on dopaminergic neurons, which can lead to a Parkinson's disease (PD)-like syndrome. Epigenetics regulates gene expression dynamically through DNA methylation, histone post-translational modification, microRNA (miRNA) interaction, and RNA methylation. MicroRNA (miRNA), representing one of the primary epigenetic mechanisms responsible for regulating gene expression, plays a crucial role in maintaining normal cellular function, while dysregulation of miRNA expression has been observed in PD. This study aims to investigate the regulatory mechanisms of miRNA in ATR exposure. The results show that ATR-exposure significantly upregulates the expression level of miR-217-5p. Both miR-217-5p overexpression and ATR exposure is able to trigger the autophagy process and apoptosis. Conversely, inhibiting the expression of miR-217-5p can reverse the levels of ATR-induced autophagy and apoptosis. Moreover, ATR causes damage to dopaminergic neurons, as indicated by the altered expression of tyrosine hydroxylase and α-synuclein. Taken together, these results suggest that ATR-induced autophagy can accelerate the progression of neurodegenerative diseases and that miR-217-5p is probably an important target involved in ATR-induced dopaminergic damage, shedding important light on the development of a novel strategy for treating neurodegenerative diseases.

The landscape ofmicroRNA interaction annotation: analysis ofthree rare disorders as a case study.

In recent years, a huge amount of data on ncRNA interactions has been described in scientific papers and databases. Although considerable effort has been made to annotate the available knowledge in public repositories, there are still significant discrepancies in how different resources capture and interpret data on ncRNA functional and physical associations. In the present paper, we present a collection of microRNA-mRNA interactions annotated from the scientific literature following recognized standard criteria and focused on microRNAs, which regulate genes associated with rare diseases as a case study. The list of protein-coding genes with a known role in specific rare diseases was retrieved from the Genome England PanelApp, and associated microRNA-mRNA interactions were annotated in the IntAct database and compared with other datasets. RNAcentral identifiers were used for unambiguous, stable identification of ncRNAs. The information about the interaction was enhanced by a detailed description of the cell types and experimental conditions, providing a computer-interpretable summary of the published data, integrated with the huge amount of protein interactions already gathered in the database. Furthermore, for each interaction, the binding sites of the microRNA are precisely mapped on a well-defined mRNA transcript of the target gene. This information is crucial to conceive and design optimal microRNA mimics or inhibitors to interfere in vivo with a deregulated process. As these approaches become more feasible, high-quality, reliable networks of microRNA interactions are needed to help, for instance, in the selection of the best target to be inhibited and to predict potential secondary off-target effects. Database URL https://www.ebi.ac.uk/intact.

Multi-omics analysis reveals the interaction of gut microbiome and host microRNAs in ulcerative colitis

Background Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract that co-occurs with gut microbiota dysbiosis; however, its etiology remains unclear. MicroRNA (miRNA)-microbiome interactions play an essential role in host health and disease. Methods To investigate the gut microbiome and host miRNA profiles in colitis, we used a Dextran Sulfate Sodium (DSS)-induced ulcerative colitis (UC) model. Metagenomic sequencing and metabolome profiling were performed to explore typical microbiota and metabolite signatures in colitis, whereas mRNA and miRNA sequencing were used to determine differentially expressed miRNAs and their target genes in the inflamed colon. Results A total of 986 miRNAs were identified between the two groups, with 41 upregulated and 21 downregulated miRNAs in colitis mice compared to the control group. Notably, the target genes of these significantly altered miRNAs were primarily enriched in the immune and inflammation-related pathways. Second, LEfSe analysis revealed bacterial biomarkers distinguishing the two groups, with significantly higher levels of commonly encountered pathogens such as Escherichia coli and Shigella flexneri in the UC group, whereas beneficial species such as Bifidobacterium pseudolongum were more abundant in the control group. Microbiota metabolites histamine, N-acetylhistamine, and glycocholic acid were found to be downregulated in colitis mice. Spearman correlation further revealed the potential crosstalk between the microbiota profile and colonic miRNA, revealing the possibility of microbiome–miRNA interactions involved in IBD development. Conclusions Our data reveal the relationships between multi-omic features during UC and suggest that targeting specific miRNAs may provide new avenues for the development of effective miRNA-based therapeutics.