microRNA Expression Research Articles

Impact of Smoking on MicroRNAs in Significant Coronary Artery Disease.

Given the importance of coronary artery disease (CAD) and the range of cardiovascular disease phenotypes in smokers, as well as the potential genetic and epigenetic factors, we were motivated to explore the impact of smoking on some selected microRNAs associated with significant CAD. A total of 60 individuals were selected in four groups including non-smoker without significant CAD (S-A-), non-smokers with significant CAD (S-A+), smokers without significant CAD (S+A-) and smokers with significant CAD (S+A+). Micro-RNA expression was investigated using real-time PCR. General linear model was used to calculate fold change (FC) considering SA- as the reference group. For mir-34a, down-regulation was observed in S+A- (FC =0.13, P =0.007) and S+A+ (FC =0.23, P =0.036) groups. For mir-126-3p, down-regulation was observed in S-A+ group (FC =0.05, P =0.024). For mir-199, up-regulation was observed for S+A- group (FC =9.38, P =0.007). The only significant interaction between pack-years of smoking and number of significantly narrowed vessels (≥75% stenosis) was for mir-199 which was in favor of down-regulation (P =0.006), while the main effects were in favor of up-regulation (P <0.05). Mir-34a expression may be affected by smoking, whereas mir-126-3p expression may be affected by atherosclerosis, the most common reason of CAD. The significant down-regulation of mir-199 for the interaction of smoking dose and severity of CAD was a notable finding showing the harmful consequence of this interaction. Further studies are needed for this micro-RNA.

Infection by the Lungworm Rhabdias pseudosphaerocephala Affects the Expression of Immune-Related microRNAs by Its Co-Evolved Host, the Cane Toad Rhinella marina.

Parasites may suppress the immune function of infected hosts using microRNAs (miRNAs) to prevent protein production. Nonetheless, little is known about the diversity of miRNAs and their mode(s) of action. In this study, we investigated the effects of infection by a parasitic lungworm (Rhabdias pseudosphaerocephala) on miRNA and mRNA expression of its host, the invasive cane toad (Rhinella marina). To investigate the cane toad's innate and adaptive immune response to this parasite, we compared miRNA and mRNA expression in naïve toads that had never been infected by lungworms to toads that were infected with lungworms for the first time in their lives, and toads that were infected the second time in their lives (i.e., had two consecutive infections). In total, we identified 101 known miRNAs and 86 potential novel miRNAs. Compared to uninfected and single-infection toads, multiple-infection animals drastically downregulated three miRNAs. These miRNAs were associated with gene pathways related to the immune response, potentially reflecting the immunosuppression of cane toads by their parasites. Infected hosts did not respond with substantially differential mRNA transcription; only one gene was differentially expressed between control and single-infection hosts. Our study suggests that miRNA may play an important role in mediating host-parasite interactions in a system in which an ongoing range expansion by the host has generated substantial divergence in host-parasite interactions.

The Impact of Alcohol-Induced Epigenetic Modifications in the Treatment of Alcohol use Disorders.

Alcohol use disorders are responsible for 5.9% of all death annually and 5.1% of the global disease burden. It has been suggested that alcohol abuse can modify gene expression through epigenetic processes, namely DNA and histone methylation, histone acetylation, and microRNA expression. The alcohol influence on epigenetic mechanisms leads to molecular adaptation of a wide number of brain circuits, including the hypothalamus-hypophysis-adrenal axis, the prefrontal cortex, the mesolimbic-dopamine pathways and the endogenous opioid pathways. Epigenetic regulation represents an important level of alcohol-induced molecular adaptation in the brain. It has been demonstrated that acute and chronic alcohol exposure can induce opposite modifications in epigenetic mechanisms: acute alcohol exposure increases histone acetylation, decreases histone methylation and inhibits DNA methyltransferase activity, while chronic alcohol exposure induces hypermethylation of DNA. Some studies investigated the chromatin status during the withdrawal period and the craving period and showed that craving was associated with low methylation status, while the withdrawal period was associated with elevated activity of histone deacetylase and decreased histone acetylation. Given the effects exerted by ethanol consumption on epigenetic mechanisms, chromatin structure modifiers, such as histone deacetylase inhibitors and DNA methyltransferase inhibitors, might represent a new potential strategy to treat alcohol use disorder. Further investigations on molecular modifications induced by ethanol might be helpful to develop new therapies for alcoholism and drug addiction targeting epigenetic processes.

BIOM-33. INVESTIGATING MIR-21 AS A NON-INVASIVE PROGNOSTIC BIOMARKER IN GLIOMA PATIENTS IN RESOURCE CONSTRAINT SETTINGS

Abstract BACKGROUND Glioma treatment remains challenging due to high recurrence rates and resistance to treatment. Diagnosis and follow-up in resource-constrained regions often leads to significant patient attrition. Serum microRNA (miRNA) expression profiles are shown to be expressed in tumor tissue and peripheral samples, offering a pathway for non-invasive, repetitive liquid biopsies. miR-21 shows promise in many populations; however, there is a dearth of data from our region. METHODOLOGY we collected 89 intraoperative tumor tissue samples, 42 pre- and post-operative serum samples from glioma patients, and included 10 control tissue samples along with 8 normal serum samples and analyzed for miR-21 expression through qPCR. Serum samples were collected before tumor resection and post-surgery (pre- and post-operative). Correlational analysis with molecular markers IDH, Ki-67, ATRX, p53, and survival curves through the Kaplan-Meier method were calculated in high and low miR-21 expression groups, The hazard ratio was quantitatively determined using Cox regression analysis, considering both univariate associations and multivariate correlations with clinical parameters. RESULTS miR-21 expression in tissue increased with higher grades of glioma (p=0.00064), of patients above 50 years (p=0.0027), and shows a positive correlation with tumor volume (r= 0.22, p=0.081). IDH-wildtype (p=2.06e-03) and high Ki-67 (p=2.50e-03) expression in tumors showed significant upregulation of miR-21 compared to IDH-mutant and low Ki-67. Patients with low miR-21 expression had significantly longer overall survival (OS) than patients with high miR-21 expression (p =0.006). Quantitative hazard analysis indicates that patients in the high expression group have a 2.77 times higher risk of mortality (95% CI: upper - 0.19, lower - 0.92), in comparison to patients in the low expression group (p= 0.008). CONCLUSION Our findings validate the future utility of miR-21 as a serum assay to help diagnose and assess treatment response in different grades of glioma, within our population. Keywords: Glioma, Biomarker, Molecular markers, Liquid biopsy

Extracellular Vesicle microRNAs as Possible Liquid Biopsy Markers in HNSCC—A Longitudinal, Monocentric Study

Background: Biomarkers for HNSCC are still lacking. Biomolecules obtained via liquid biopsy are being investigated for diagnosis, prognosis, and therapy monitoring, including extracellular vesicles (EVs) and EV-cargo, e.g., proteins, RNA, and microRNA. This study aims to understand localization-dependent EV-microRNA expression in blood sera, their dynamics over time (12 months FU), and insights into their potential in diagnostics and therapy monitoring. Methods: Via liquid biopsy, blood serum was taken from 50 patients with HNSCC and 16 controls. Extracellular vesicles were isolated from serum by precipitation, and the contained microRNA-21, -1246, -200c, -let-7a, -181a, and -26a were amplified by reverse transcription and determined with real-time PCR. Expression ratios (HNSCC to healthy controls) were collated with the patients’ clinical parameters. A second liquid biopsy was carried out avg. 12 months later in the tumor aftercare. A sub-analysis with the Oropharynx subsite was implemented. Results: EV-mir-21, -let-7a, and -181a were 2.5–3-fold higher expressed in HPV/p16+ than in HPV/p16- HNSCC. Different expressions of EV-mir-181a and -26a could be demonstrated depending on the therapy modality. Conclusions: EV-microRNA could be a promising biomarker in the diagnosis and therapy monitoring of HNSCC. A systematic comparison of EV- and tissue microRNA expression in different HNSCC-subsites is needed.

The role of viral infection in implantation failure: direct and indirect effects.

Implantation is the key initial complex stage of pregnancy. Several factors are involved in implantation, but acute and controlled inflammation has been shown to play as a key role. On the other hand, the role of viral infections in directly infecting blastocyst and trophoblast and inducing chronic and uncontrolled inflammation and disrupting microRNAs expression can make this review strongly attractive and practical. We aim to provide an overview of viral infections as the potential etiology of unsuccessful implantation pathophysiology through alteration of the cellular and molecular endometrial microenvironment. Based on our search, this is the first review to discuss the role of inflammation associated with viral infection in implantation failure.

Expression of Salivary miRNAs, Clinical, and Demographic Features in the Early Detection of Gastric Cancer: A Statistical and Machine Learning Analysis.

Gastric cancer ranks as one of the top five deadliest cancers worldwide and is often diagnosed at late stages. Analysis of saliva may provide a non-invasive approach for detection of malignancies in organs associated with the oral cavity. This research aims to analyze salivary microRNA expression together with clinical and demographic features with the aim of diagnosing gastric cancer. The study included 19 patients with early-stage gastric cancer and 19 healthy controls. Saliva samples were collected and processed for RNA isolation. Salivary expression of miR-223-3p and miR-21-5p were measured using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curves were generated to evaluate the accuracy of diagnostic models. Machine learning algorithms, multiple logistic regression, and principal component analysis (PCA) were used to assess the predictive power of miRNAs in conjunction with clinical-demographic features. Significant upregulation of miR-223-3p and downregulation of miR-21-5p in saliva were observed in patients with gastric cancer. The area under ROC curve (AUC) values for salivary miR-21-5p, salivary miR-223-3p, and their multiple logistic regression were determined to be 0.723, 0.791, and 0.850, respectively. The AUC for multiple logistic regression model was 0.919. The PCA model led to the highest diagnostic odds ratio (DOR) of 134.33 (sensitivity = 0.785, specificity = 1.00, AUC = 903). Application of machine learning methods, and in particular a random forest algorithm, showed high accuracy in diagnosing patients with gastric cancer (sensitivity = 1.00, specificity = 0.857, AUC = 0.93). The application of validated salivary diagnostics in clinical practice could help facilitate earlier diagnosis of gastric cancer and improve medical outcome. Expression of miR-21 and miR-223-3p in saliva together with clinical and demographic features, appears promising in screening for GC.

Data normalization of plasma miRNA profiling from patients with COVID-19

When using the reverse-transcription quantitative polymerase chain reaction (RT-qPCR) technique for quantitative assessment of microRNA (miRNA) expression, normalizing data using a stable endogenous gene is essential; however, no universally adequate reference gene exists. Therefore, in this study, we aimed to determine, via the RNA-Seq technique, the most adequate endogenous normalizer for the expression assessment of plasma miRNAs in patients with coronavirus disease 2019 (COVID-19). Two massive sequencing procedures were performed (a) to identify differentially expressed miRNAs between patients with COVID-19 and healthy volunteers (n = 12), and (b) to identify differentially expressed miRNAs between patients with severe COVID-19 and those with mild COVID-19 (n = 8). The endogenous normalizer candidates were selected according to the following criteria: (1) the miRNA must have a fold regulation = 1; (2) the miRNA must have a p-value > 0.990; and (3) the miRNAs that were discovered the longest ago should be selected. Four miRNAs (hsa-miR-34a-3p, hsa-miR-194-3p, hsa-miR-17-3p, and hsa-miR-205-3p) met all criteria and were selected for validation by RT-qPCR in a cohort of 125 patients. Of these, only hsa-miR-205-3p was eligible endogenous normalizers in the context of COVID-19 because their expression was stable between the compared groups.

Analysis of Polyphyllin II alters microRNA expression profile in lung cancer A549 cells

Non-small cell lung cancer (NSCLC) is a malignant tumor that threatens the whole world, previous studies found that Polyphyllin II (PPII) can suppress NSCLC cells growth, exhibits significant antitumor activity. MicroRNAs (miRNAs) can regulate the expression of other genes and play a crucial role in the prevention and development of cancer. However, the miRNA portrait of ginsenoside PPII-treated NSCLC A549 cells has not yet been studied. In this work, miRNA-seq analysis was used to determine the changes in miRNA expression profile of NSCLC A549 cells PPII-treaded. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on differentially expressed miRNA target genes. Then, predicted the target genes of miRNA and performed functional enrichment analysis on them. We identified 58 up-regulated and 24 down-regulated miRNAs displaying changes their expression in PPII treated A549 cells were greater than 2-fold. In addition, the expression levels of miRNAs were validated by real-time PCR. Therefore, this work has a certain promoting effect on the study of the anti-cancer mechanism of PPII in lung cells.

Analysis of Differential microRNA Expression in the Hippocampus of Scopolamine-Induced Amnesic Mouse Model.

Amnesia is characterized by memory deficits linked to various neurodegenerative pathologies and can be induced by the administration of scopolamine, a cholinergic antagonist. Scopolamine-induced amnesia is a well-studied pharmacological animal model that simulates memory impairment caused by aging, brain illnesses, neuropathologies, and trauma. However, the molecular mechanism of amnesia, more importantly in terms of microRNA (miRNA) regulation, is not well understood. Therefore, this study aimed to analyze miRNA profiles in the hippocampus of both control mice and those treated with scopolamine (amnesic mice). Initially, a short cDNA library was prepared for each sample and then sequenced on the Illumina platform. Among the total differentially expressed miRNAs, 113 were significantly upregulated and 96 were downregulated in the scopolamine group in comparison to the control group. Ten upregulated and ten downregulated miRNAs were validated to confirm the reliability of the sequencing results using qRT-PCR (quantitative real-time PCR). Furthermore, we performed a target prediction analysis intersecting the results from TargetScan, miRDB (miRNA database), and Miranda to analyze the targets of the dysregulated miRNAs. We also conducted a pathway analysis to investigate the molecular, cellular, and biological functions of these targets. miRNA‒target interactions were found to play roles in various signaling pathways during amnesia. These results provide an initial insight for the contribution of miRNAs to scopolamine-induced amnesia, as well as their possible application as markers of disease pathology.

Characteristics of Pulmonary Inflammation in Patients with Different Forms of Active Tuberculosis.

Targeted treatment of tuberculosis-associated lung damage requires an understanding of the precise mechanisms of immunopathology. A major obstacle to the longitudinal study of tuberculosis (TB) immunopathogenesis in humans is the lack of serial lung biopsies during disease progression and treatment, which could be used to characterize local immune pathways involved in tissue damage. Understanding of the immunobiology of lung tissue damage in tuberculosis has largely been based on animal models. Our study looked for signs of inflammation in TB patients' lung biopsies. Results were compared between a site of infection and relatively healthy tissue outside the site. The most significant differences in the expression of microRNAs (miRs) and cytokine/chemokines were observed between the non-decayed tuberculoma and the surrounding parenchyma. In addition, these parameters showed almost no differences between the cavitary wall and surrounding tissue. This is an indication that the inflammatory process is more prevalent in fibrotic cavitary tuberculosis (FCT). In FCT subjects, no difference was observed between the cavity wall and the parenchyma in the production of key inflammatory factors such as IL-6, IL-11, IL-17, and IFNγ. This is an indication that the limits of the inflammatory response are broader in FCT. The expression levels of miR-191, miR-193a, miR-222, miR-223, miR-18, miR-155, miR-376c, miR-26a, miR-150, and miR-124 were not significantly different between the cavernous wall and lung tissue in patients with FCT, further confirming the spread of inflammatory and destructive processes beyond the focus of infection.

Unveiling the Predictive Model for Macrovascular Complications in Type 2 Diabetes Mellitus: microRNAs Expression, Lipid Profile, and Oxidative Stress Markers.

To assay new circulating markers related to macrovascular complications (MVC) in type 2 diabetes mellitus (T2DM), we carried out a descriptive cross-sectional study. We recruited 30 controls (CG), 34 patients with T2DM (DG), and 28 patients with T2DM and vascular complications (DG+C); among them, 22 presented MVC. Peripheral blood was used to determine redox status (superoxide dismutase, SOD; catalase, CAT; glutathione reductase, GRd; glutathione peroxidase, GPx; glucose-6-phosphate dehydrogenase, G6PD) and markers of oxidative damage (advanced oxidation protein products, AOPP; lipid peroxidation, LPO), nitrite levels in plasma (NOx). Inflammatory markers (IL-1β, IL-6, IL-10, IL-18, MCP-1, TNF-α) and the relative expression of c-miRNAs were analyzed. The real-time PCR results showed that the expressions of miR-155-5p, miR-21-5p, miR-146a-3p, and miR-210-3p were significantly higher in the DG group compared to the CG. The DG+C group presented statistically relevant differences with CG for four miRs: the increased expression of miR-484-5p, miR-21-5p, and miR-210-3p, and decreased expression of miR-126a-3p. Moreover, miR-126a-3p was significantly less expressed in DG+C compared to DG. The application of binary logistic regression analysis and construction of receiving operator characteristic curves (ROC) revealed two models with high predictive values for vascular complications presence: (1) HbAc1, creatinine, total cholesterol (TC), LPO, GPx, SOD, miR-126, miR-484 (Exp(B) = 0.926, chi2 = 34.093, p < 0.001; AUC = 0.913). (2) HbAc1, creatinine, TC, IL-6, LPO, miR-126, miR-484 (Exp(B) = 0.958, Chi2 = 33.863, p < 0.001; AUC = 0.938). Moreover, our data demonstrated that gender, TC, GPx, CAT, and miR-484 were associated with MVC and exhibited higher predictive values (Exp(B) = 0.528, p = 0.024, Chi2 = 28.214, AUC = 0.904) than classical variables (Exp(B) 0.462, p = 0.007, Chi2 = 18.814, AUC = 0.850). miR-126, miR-484, IL-6, SOD, CAT, and GPx participate in vascular damage development in the studied diabetic population and should be considered for future studies.

The Landscape of microRNAs in Bone Tumor: A Comprehensive Review in Recent Studies.

Cancer, the second greatest cause of mortality worldwide, frequently causes bone me-tastases in patients with advanced-stage carcinomas such as prostate, breast, and lung cancer. The existence of these metastases contributes to the occurrence of skeletal-related events (SREs), which are defined by excessive pain, pathological fractures, hypercalcemia, and spinal cord com-pression. These injurious incidents leave uncomfortably large holes in each of the cancer patient's life quality. Primary bone cancers, including osteosarcoma (OS), chondrosarcoma (CS), and Ewing's sarcoma (ES), have unclear origins. MicroRNA (miRNA) expression patterns have been changed in primary bone cancers such as OS, CS, and ES, indicating a role in tumor development, invasion, metastasis, and treatment response. These miRNAs are persistent in circulation and ex-hibit distinct patterns in many forms of bone tumors, making them potential biomarkers for early detection and treatment of such diseases. Given their crucial regulatory functions in various bio-logical processes and conditions, including cancer, this study aims to look at miRNAs' activities and possible contributions to bone malignancies, focusing on OS, CS, and ES. In conclusion, miRNAs are valuable tools for diagnosing, monitoring, and predicting OS, CS, and ES outcomes. Further research is required to fully comprehend the intricate involvement of miRNAs in these bone cancers and to develop effective miRNA-based treatments.

Assessing the use of blood microRNA expression patterns for predictive diagnosis of myxomatous mitral valve disease in dogs

Assessing the use of blood microRNA expression patterns for predictive diagnosis of myxomatous mitral valve disease in dogs

MiR-199a-5p aggravates renal ischemia-reperfusion and transplant injury by targeting AKAP1 to disrupt mitochondrial dynamics.

Renal ischemia-reperfusion injury (IRI) is a complex pathophysiological process and a major cause of delayed graft function (DGF) after transplantation. MicroRNA (miRNA) has important roles in the pathogenesis of IRI and may represent promising therapeutic targets for mitigating renal IRI. miRNA sequencing was performed to profile microRNA expression in mouse kidneys after cold storage and transplantation (CST). Lentivirus incorporating a miR-199a-5p modulator was injected into mouse kidney in situ before syngenetic transplantation and unilateral IRI to determine the effect of miR-199a-5p in vivo. miR-199a-5p mimic or inhibitor was transfected cultured tubular cells before ATP depletion recovery treatment to examine the role of miR-199a-5p in vitro. Sequencing data and microarray showed upregulation of miR-199a-5p in mice CST and human DGF samples. Lentivirus incorporating a miR-199a-5p mimic aggravated renal IRI, and protective effects were obtained with a miR-199a-5p inhibitor. Treatment with the miR-199a-5p inhibitor ameliorated graft function loss, tubular injury, and immune response after CST. In vitro experiments revealed exacerbation of mitochondria dysfunction upon ATP depletion and repletion model in the presence of the miR-199a-5p mimic, whereas dysfunction was attenuated when the miR-199a-5p inhibitor was applied. miR-199a-5p was shown to target A-kinase anchoring protein 1 (AKAP1) by double luciferase assay and miR-199a-5p activation reduced dynamin-related protein 1 (Drp1)-s637 phosphorylation and mitochondrial length. Overexpression of AKAP1 preserved Drp1-s637 phosphorylation and reduced mitochondrial fission. miR-199a-5p activation reduced AKAP1 expression, promoted Drp1-s637 dephosphorylation, aggravated the disruption of mitochondrial dynamics, and contributed to renal IRI.NEW & NOTEWORTHY This study identifies miR-199a-5p as a key regulator in renal ischemia-reperfusion injury through microRNA sequencing in mouse models and human delayed graft function. miR-199a-5p worsens renal IRI by aggravating graft dysfunction, tubular injury, and immune response, while its inhibition shows protective effects. miR-199a-5p downregulates A-kinase anchoring protein 1 (AKAP1), reducing dynamin-related protein 1 (Drp1)-s637 phosphorylation, increasing mitochondrial fission, and causing dysfunction. Targeting the miR-199a-5p/AKAP1/Drp1 axis offers therapeutic potential for renal IRI, as AKAP1 overexpression preserves mitochondrial integrity by maintaining Drp1-s637 phosphorylation.

The MicroRNA miR-223 Constrains Colitis-associated Tumorigenesis by Limiting Myeloid Cell Infiltration and Chemokine Expression.

Aberrant intestinal inflammation plays a critical role in the development of colitis-associated colorectal cancer (CAC), yet the mechanisms controlling tumor development by the myeloid immune compartment are not fully understood. Although altered microRNA expression is observed in CAC, it is also unclear how myeloid-specific microRNAs impact the inflammatory process that underpins the continuum from ulcerative colitis to tumorigenesis. In this study, we report that miR-223 acts to limit myeloid-driven inflammation in the azoxymethane (AOM)-dextran sodium sulfate (DSS) model of CAC in mice. In this model, miR-223-/y mice present with significantly larger tumors with an enhanced proliferative signature. Immunoprofiling showed that miR-223-/y mice have significantly increased colonic myeloid immune infiltrate (neutrophils, monocytes, and macrophages) following AOM-DSS. This was accompanied by an increased inflammatory chemokine and cytokine signature for monocytes and neutrophils. Bone marrow chimera studies demonstrate that myeloid-expressed miR-223 is responsible for the enhanced tumor proliferation and inflammatory response. RNA sequencing identified several pathways that could be contributing to the development of CAC in miR-223-/y mice, including the IL-6/IL-17a cytokine family and STAT3 signaling. Lastly, neutrophil depletion with an anti-GR1 Ab (Ly6G/Ly6C) during the initial phase of the AOM-DSS model reduced the tumor burden in miR-223-/y mice. Collectively, our data indicate that miR-223 is an important regulator of mucosal inflammation and acts to constrain the progression from ulcerative colitis to CAC by limiting myeloid-associated inflammation.

DNA methylation and non-coding RNAs in metabolic disorders: Epigenetic Roles of Nutrients, Dietary Patterns and Weight Loss Interventions for Precision Nutrition.

Dysregulation of epigenetic processes and abnormal epigenetic profiles are associated with various metabolic disorders. Nutrition, as an environmental factor, can induce epigenetic changes through both direct exposure and transgenerational inheritance, continuously altering gene expression and shaping the phenotype. Nutrients consumed through food or supplementation, such as vitamin B12, folate, vitamin B6, and choline, play a pivotal role in DNA methylation, a critical process for gene regulation. Additionally, there is mounting evidence that the expression of non-coding RNAs (ncRNAs) can be modulated by the intake of specific nutrients and natural compounds, thereby influencing processes involved in the onset and progression of metabolic diseases. Evidence suggests that dietary patterns, weight-loss interventions, nutrients and nutritional bioactive compounds can modulate the expression of various miRNAs and DNA methylation levels, contributing to development of metabolic disorders such as obesity and type 2 diabetes. Furthermore, several studies have proposed that DNA methylation and microRNA (miRNA) expression could serve as biomarkers for the effects of weight-loss programs. Despite ongoing debate regarding the effects of nutrient supplementation on DNA methylation levels and the expression of ncRNAs, certain DNA methylation marks and ncRNA expressions might predict the risk of metabolic disorders and act as biomarkers for forecasting the success of therapies within the framework of precision medicine and nutrition. The role of DNA methylation and miRNA expression as potential mediators of the effects of weight loss underscores their potential as biomarkers for the outcomes of weight loss programs. This highlights the influence of dietary patterns and weight-loss interventions on the regulation of miRNA expression and DNA methylation levels, suggesting an interaction between these epigenetic factors and the body's response to weight loss.

Diagnosis of Colorectal Cancer and Adenomatous Polyps of the Colon Based on the Level of MicroRNA Expression in the Mucous Membrane (Pilot Clinical Study)

Diagnosis of Colorectal Cancer and Adenomatous Polyps of the Colon Based on the Level of MicroRNA Expression in the Mucous Membrane (Pilot Clinical Study)

Different microRNA expression in the right ventricular outflow tract myocardium of tetralogy of Fallot

Abstract Background When repairing tetralogy of Fallot (TOF), there are two surgical options according to the size of the pulmonary valve: transannular patch repair and valve-preserving repair. Since the development of the pulmonary valve depends on the degree of obstruction of the right ventricular outflow tract (RVOT), molecular profiles of the RVOT muscles may be associated with the surgical decision. As a recent study shows altered microRNA expression of the right ventricular myocardium even in TOF patients, microRNA expression of the RVOT infundibular muscle may be different between the two procedures. Purpose To evaluate differences in microRNA expression levels of RVOT infundibular muscles between the transannular patch repair and valve-preserving repair groups. Methods Surgically resected infundibular muscles from TOF patients are frozen in liquid nitrogen and stored in our hospital biobank. Nine samples collected between August 2020 and July 2022 were used in this study. Five patients underwent a valve-preserving repair and the others underwent a transannular patch repair. Six patients were female and mean age at operation was 453 ± 240 days. These samples were homogenized and total RNA including microRNAs were extracted. MicroRNA expression levels were measured using a microRNA array capable of detecting over 2000 microRNAs simultaneously. Results 1171 microRNAs were detected in all nine samples. The expression levels of 22 microRNAs were significantly different between the transannular patch repair group and the valve-preserving repair group (P&amp;lt;0.05). The expression levels of 19 microRNAs were significantly higher in the transannular patch repair group and the others were significantly higher in the valve-preserving repair group. More than 2-fold changes were observed in 2 microRNAs between the transannular patch repair and valve-preserving repair groups. Conclusion MicroRNA expression of RVOT infundibular muscle differs between the transannular patch repair and valve-preserving repair groups. Therefore, microRNA analysis will be useful to evaluate the pathophysiology of TOF. In addition, microRNAs may become a useful biomarker for surgical decision making in TOF.

RNA-seq validation of microRNA expression signatures for precision melanoma diagnosis and prognostic stratification

BackgroundNew diagnostic tools are needed to improve the diagnosis and risk stratification of cutaneous melanoma. Disease-specific microRNA signatures have been previously described via NanoString profiling of solid biopsy tissue and plasma. This study validated these signatures via next-generation sequencing technology and compared their performance against clinical metrics and other published melanoma signatures.MethodsRNA from 64 plasma and 60 FFPE biopsy samples from individuals with invasive melanoma or related benign/control phenotypes was extracted and enriched for microRNA. RNA sequencing was performed to compute MEL38/MEL12 signature scores. The results were evaluated with published NanoString and RNA sequencing datasets, comprising 548 solid tissue samples and 217 plasma samples, to predict disease status and patient outcome.ResultsThe MEL38 diagnostic signature classifies patients into discrete diagnostic groups via RNA sequencing in either solid tissue or plasma (P < 0.001). In solid tissue, the prognostic MEL12 signature stratifies patients into low-, intermediate- and high-risk groups, independent of clinical covariates. The hazard ratios for 10-year overall survival, based on observed survival intervals, were 2.2 (MEL12 high-risk vs low-risk, P < 0.001) and 1.8 (intermediate-risk vs low-risk, P < 0.001), outperforming other published prognostic models. MEL12 also exhibited prognostic significance in the plasma of 42 patients with invasive disease.ConclusionsThe MEL38 and MEL12 signatures can be assessed in either solid tissue or plasma using RNA-seq and are strong predictors of disease state and patient outcome. Compared with other genomic methods, MEL12 was shown to be the strongest predictor of poor prognosis. MicroRNA expression profiling offers objective, accurate genomic information about a patient’s likelihood of invasive melanoma and prognosis.