Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes
Project description:MicroRNAs (miRNAs) in oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) play a pivotal role in modulating intercellular communications between tumor cells and other cells in microenvironment, thereby influencing tumor progression and the efficacy of therapeutic interventions. However, a comprehensive inventory of these secretory miRNAs in sEVs and their biological and clinical implications remains elusive. This study aims to profile the miRNA content of OSCC cell lines sEVs and computationally elucidate their biological and clinical relevance. We conducted miRNA sequencing to compare the miRNA profiles of OSCC cells and their corresponding sEVs. Our motif enrichment analysis identified specific sorting motifs that are implicated in either cellular retention or preferential sEVs secretion. Target cell analysis suggested that the sEVs miRNAs potentially interact with various immune cell types, including natural killer cells and dendritic cells. Additionally, we explored the clinical relevance of these miRNAs by correlating their expression levels with TNM stages and patient survival outcomes. Intriguingly, our findings revealed that a distinct sEVs miRNA signature is associated with lymph node metastasis and poorer survival in patients in TCGA-HNSC dataset. Collectively, this research furthers our understanding of the miRNA sorting mechanisms in OSCC and underscores their clinical implications.
Project description:To discover miRNAs implicate in PAPS pathogenesis, we isolated sEVs from plasma of PAPS patients, aPL patients (patients with positive antiphospholipid antibodies without thrombotic or obstretic complications) and control. Then, we extracted RNA total and we performed miRNA-sequencing.
Project description:Ischemic cardiomyopathy (ICM), caused by acute myocardial infarction (AMI), is the most common type of chronic heart failure (HF). Treg cells, maintaining peripheral immune tolerance, are dysfunctional in ICM mice. The mechanism of dysfunctional Treg cells in ICM remains unclear. Furthermore, small extracellular vesicles (sEVs) are significant in intracellular communication and tissue homeostasis. This study tends to illustrate whether plasma sEVs of ICM promote the dysfunctional state of Treg cells through miRNA and thus aggravate cardiac remodeling.In ICM patients, the number of Treg cells was increased while Foxp3 mean fluorescence intensity (MFI) was decreased in peripheral blood, indicating a dysfunctional phenotype of Treg cells. miR-223-3p, identified by sequencing using plasma sEVs of ICM patients, was upregulated and negatively correlated with blood Treg cell number. Additionally, the number of cardiac Treg cells of ICM mice was increased while Foxp3 MFI was decreased. Furthermore, plasma sEVs from ICM mice aggravate ventricular remodeling in mice post-AMI. Besides, ICM-sEVs decreased the number of Treg cells while miR-223-3p knockdown increased the number of them and promoted the expression of Foxp3 in vitro.Plasma sEVs of ICM aggravate ventricular remodeling post-AMI through miR-223-3p-mediated Treg cells dysfunction in ICM.
Project description:To explore the miRNA expression profiles between HBV-related Hepatocellular carcinoma and no HBV-related Hepatocellular carcinoma To performe microarray analysis to detect the miRNA expression profiles between HBV-related Hepatocellular carcinoma and no HBV-related Hepatocellular carcinoma
