Project description:Major depressive disorder (MDD) is the leading cause of disability worldwide. There is an urgent need for objective biomarkers to diagnose this highly heterogeneous syndrome, assign treatment, and evaluate treatment response and prognosis. MicroRNAs (miRNAs) are short non-coding RNAs, which are detected in body fluids that have emerged as potential biomarkers of many disease conditions. The present study explored the potential use of miRNAs as biomarkers for MDD and its treatment. We profiled the expression levels of circulating blood miRNAs from mice that were collected before and after exposure to chronic social defeat stress (CSDS), an extensively validated mouse model used to study depression, as well as after either repeated imipramine or single-dose ketamine treatment. We observed robust differences in blood miRNA signatures between stress-resilient and stress-susceptible mice after an incubation period, but not immediately after exposure to the stress. Furthermore, ketamine treatment was more effective than imipramine at re-establishing baseline miRNA expression levels, but only in mice that responded behaviorally to the drug. We identified the red blood cell-specific miR-144-3p as a candidate biomarker to aid depression diagnosis and predict ketamine treatment response in stress-susceptible mice and MDD patients. Lastly, we demonstrate that systemic knockdown of miR-144-3p, via subcutaneous administration of a specific antagomir, is sufficient to reduce the depression-related phenotype in stress-susceptible mice. RNA-sequencing analysis of blood after such miR-144-3p knockdown revealed a blunted transcriptional stress signature as well. These findings identify miR-144-3p as a novel target for diagnosis of MDD as well as for antidepressant treatment, and enhance our understanding of epigenetic processes associated with depression.
Project description:miR-144/451 cluster is highly conversed in different species, miRbase database shows miR-144/451 cluster is constituted by miR-144-3p, miR-144-5p, miR-451a. Low-expression of miR-144/451 was closely related with the risk for esophageal cancer We used microarrays to identify the differentially expressed genes in ECa9706 over expressing miR-144/451 cluster
Project description:Advanced age represents one of the major risk factors for Parkinson’s Disease. Recent studies posit a role for microRNAs in Parkinson’s Disease and it is well established that microRNAs are remodelled during ageing, but the relationship between the two processes have not been clarified yet. The aim of the present study is to unravel the relevance of microRNAs as biomarkers of Parkinson’s Disease within the ageing framework. We used Next Generation Sequencing to profile serum microRNAs from samples informative for Parkinson’s Disease (recently diagnosed, drug-naïve Parkinson’s Disease patients) and healthy ageing (centenarians) plus healthy controls age-matched with Parkinson’s Disease patients. Potential candidates, emerging from the combination of differential expression and network analyses, were further validated in an independent cohort including both drug-naïve and advanced Parkinson’s Disease patients together with healthy siblings of Parkinson’s Disease patients at higher genetic risk for Parkinson’s Disease. While we did not find evidences of microRNAs co-regulated in Parkinson’s Disease and ageing, we report that hsa-miR-144-3p is consistently down-regulated in early and advanced Parkinson’s Disease and in Parkinson’s Disease siblings. Interestingly, functional analysis revealed that hsa-miR-144-3p is involved in the regulation of coagulation, a process known to be altered in Parkinson’s Disease. Our results consistently show the down-regulation of hsa-mir144-3p in early and advanced Parkinson’s Disease, robustly confirmed across a variety of analytical and experimental analyses. These results are promising, and additional research is needed to unveil the functional details of its relevance and involvement in Parkinson’s Disease.
Project description:This study aimed to elucidate the role of microRNA miR-92a-3p in the pathogenesis of adenomyosis. We focused on understanding how miR-92a-3p in exosomes derived from ectopic lesions influences the behavior of endometrial cells, DRG neurons, and Human Umbilical Vein Endothelial Cells (HUVECs), and its potential as a non-invasive diagnostic biomarker. Our findings revealed that MiR-92a-3p is significantly upregulated in exosomes derived from ectopic lesions of adenomyosis. This upregulation was associated with enhanced migration and invasion capabilities in eutopic endometrial cells, DRG neurons, and HUVECs. Furthermore, the study demonstrated a significant correlation between the levels of MiR-92a-3p in urinary exosomes and the clinical symptoms of adenomyosis, suggesting its potential as a non-invasive biomarker for the disease. This study elucidates an exosomal signaling process via miR-92a-3p that drives pathological infiltration and angiogenesis to promote adenomyosis progression. Upregulated miR-92a-3p in biofluid exosomes shows promising non-invasive biomarker potential for diagnosis and monitoring of this disease. Our findings unveil novel targets and tools for improved clinical management.
Project description:Blood samples taken from healthy controls and patients with major depression were analyzed for differences in microRNA expression. Patients were treated with either electroconvulsive therapy or ketamine and samples were again analyzed to determine if these treatments affected microRNA expression. Baseline microRNA expression profiles were studied to see if they could predict treatment response.
Project description:There is an emerging hypothesis that dilated cardiomyopathy (DCM) is a manifestation of end-stage heart failure (ESHF) resulting from “final common pathway” despite heterogeneous primary etiologies. We performed genome-wide expression profiling by means of high-density oligonucleotide microarrays using cardiac muscles from patients with DCM or specific cardiomyopathy as well as non-disease control hearts. Differentially expressed genes between ESHF and non-disease samples should include both genes reactive to heart failure (HF) and those responsible for ESHF. With the aid of samples with acute HF without DCM and those with DCM without HF (corrected with left ventricular assist device), we successfully distinguished ESHF genes from HF genes. Our findings implicate that transcriptional signature of cardiac muscle can be potentially applied as a diagnostic or prognostic tool for severe HF. Keywords: disease state analysis