Project description:To have a global picture of the targets of the mir-29b-2-5p, we assessed transcriptome changes, by deep-sequencing, of HeLa cells transfected with this miRNA or a control miRNA (cel-miR-231).
Project description:Overexpression and inhibition of miR-29 (pre-miR and anti-miR to miR-29b) in murine aortic smooth muscle cells, analysis of their secretome (conditioned media after serum starvation), n=3 for all four groups (pre-miR control, pre-miR-29b, anti-miR control, anti-miR-29b).
Project description:Chronic hepatitis B virus (HBV) infections represent a significant global health burden requiring effective therapeutic interventions. This study investigates the antiviral potential of microRNAs (miRNAs) targeting the HBV entry receptor, sodium-taurocholate cotransporting polypeptide (NTCP). Using an interferon (IFN) alpha analog, we highlighted a set of miRNAs induced in treated human hepatocytes. Notably, miR-29b-1-5p was predicted to interact with the 3’-untranslated region (3’-UTR) of NTCP. Functional analysis revealed that miR-29b-1-5p directly targeted and inhibited NTCP. Furthermore, miR-29b-1-5p overexpression significantly reduced HBV genome levels in infected hepatocytes. A rescue experiment demonstrated that miR-29b-1-5p antiviral effect was specifically mediated by NTCP targeting. In summary, these findings underscore the therapeutic potential of miR-29b-1-5p against HBV, advocating for the exploration of miRNA-based therapies in the treatment of human viral infections.
Project description:Little is known about the molecular profiling associated with the effect of cladribine in patients with multiple sclerosis (MS). Here, we aimed first to characterize the transcriptomic and proteomic profiles induced by cladribine in blood cells, and second to identify potential treatment response biomarkers to cladribine in patients with MS. PBMCs treated in vitro with cladribine were characterized by a major downregulation of gene, protein, and miRNA expression compared with the untreated cells. An intermediate pattern between the cladribine-treated and untreated conditions was observed in PBMCs treated with cladribine in its inactive form. The differential expression analysis of each dataset led to the identification of four genes and their encoded proteins, and twenty-two miRNAs regulating their expression, that were associated with cladribine treatment. Two of these genes (PPIF and NHLRC2), and three miRNAs (miR-21-5p, miR-30b-5p, and miR-30e-5p) were validated ex vivo in MS patients treated with cladribine. Conclusions: By using a combination of omics data and bioinformatics approaches we were able to identify a multiomics molecular profile induced by cladribine in vitro in PBMCs. We also identified a number of biomarkers that were validated ex vivo in PBMCs from MS patients treated with cladribine that have the potential to become treatment response biomarkers to this drug.
Project description:To explore the variation of serum microRNA expression during osteoporosis, we have employed microRNA microarray expression profiling as a discovery platform to identify microRNAs with the potential to diagnose osteoporosis from healthy and osteopenia individuals for clinical use. Whole blood from healthy, osteopenic and osteoporotic donors was collected, and the sera were separated. Twenty two microRNAs (miR-15a-5p, miR-29b-5p, miR-30c-2-3p, miR-145-5p, miR-199a-5p, miR-301a-3p, miR-424-5p, miR-497-5p, miR-526b-5p, miR-550a-5p, miR-575, miR-654-5p, miR-663a, miR-708-5p, miR-877-3p, miR-1246, miR-1260b, miR-1299, miR-1323, miR-4447, miR-4769-3p and miR-5685) were finally used for further detection of osteoporosis diagnosis.
Project description:Transcriptional profiling of human monocyte-derived dendritic cells (MDDCs), comparing cells transfected with miR-29a mimic, or miR-29b mimic, or negative control. 3 condition experiment, control versus miR-29a, and control versus miR-29b. 3 biological replicates for each condition and control.
Project description:We contrasted innate and adaptive immune responses elicited by the DNA/ALVAC/gp120/alum vaccine in non-human primates differing in age. We performed several analyses. MicroRNA profiling in Extracellular Vesicles (EVs) isolated from plasma collected prior and 1 week following vaccination identified 109 miRNAs that differed significantly between age groups at the end of immunization. Several miRNAs correlated with risk of virus acquisition in young and old animals, but none remained significant following correction for FDR. In young animals, we identified 3 miRNAs which were modified by vaccination and correlated with decreased risk of SIV acquisition (unadjusted p-values). Of these three miRNAs, two, miR-139-5p and miR-29b-1-5p, were increased by vaccination, whereas one, mir 98, decreased by vaccination. MiR-139-5p has several validated targets, including: CXCR4, important for egress of CXCR4+ cells and monocytes from bone marrow and HIV entry in target T-cells; the cAMP-specific PDE4D gene which decreases CREB1-mediated transcription by degrading cAMP; and the IGF-1/AKT/Glut1 gene receptor, central for glucose utilization and cellular metabolism. The validated target of miR-29b-1-5p is the NF-kB pathway. Mir-98 has several validated targets, inhibits IL-10 production, modulates M1-M2 polarization of macrophages towards the M1 phenotype, and its CCL2-induced downregulation increases IL-6 production. These data suggest the importance of CREB1-mediated transcription in vaccine efficacy, identified in the study, is likely assisted by miR-139-5p targeting the cAMP-degrading PDE4D gene, and downregulation of the NF-kB pathway, targeted by miR-29b-1-5p.
Project description:Elite controllers maintain HIV-1 viral loads below the limit of detection. The mechanisms responsible for this phenomenon are poorly understood. As microRNAs (miRNAs) are regulators of gene expression and some of them modulate HIV infection, we have studied the miRNA profile in plasma from HIV elite controllers and chronically infected individuals and compared against healthy donors. Several miRNAs correlate with CD4+ T cell count or with the known time of infection. No significant differences were observed between elite controllers and healthy donors; however, 16 miRNAs were different in the plasma of chronic infected versus healthy donors. In addition, levels of hsa-miR-29b-3p, hsa-miR-33a-5p and hsa-miR-146a-5p were higher in plasma from elite controllers than chronic infected and hsa-miR-29b-3p and hsa-miR-33a-5p overexpression significantly reduced the viral production in MT2 cells. Therefore, levels of circulating miRNAs might be of diagnostic and/or prognostic value for HIV infection. Additionally, hsa-miR-29b-3p and miR-33a-5p may be used in therapeutic strategies.
Project description:Transcriptional profiling of human monocyte-derived dendritic cells (MDDCs), comparing cells transfected with miR-29a mimic, or miR-29b mimic, or negative control.