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Project description:BACKGROUND:MicroRNAs (miRNAs) are small RNAs regulating gene expression post-transcriptionally. While acquired changes of miRNA and mRNA profiles in cancer have been extensively studied, little is known about expression changes of circulating miRNAs and messenger RNAs (mRNA) in monogenic constitutional anomalies affecting several organ systems, like Marfan syndrome (MFS). We performed integrated miRNA and mRNA expression profiling in blood samples of Marfan patients in order to investigate deregulated miRNA and mRNA networks in these patients which could serve as potential diagnostic and prognostic tools for MFS therapy. METHODS:MiRNA and mRNA expression profiles were determined in blood samples from MFS patients (n = 7) and from healthy volunteer controls (n = 7) by microarray analysis. Enrichment analyses of altered mRNA expression were identified using bioinformatic tools. RESULTS:A total of 28 miRNAs and 32 mRNAs were found to be significantly altered in MFS patients compared to controls (> 2.0-fold change, adjusted P < 0.05). The expression of 11 miRNA and 6 mRNA candidates was validated by RT-qPCR in an independent cohort of 26 MFS patients and 26 matched HV controls. Significant inverse correlations were evident between 8 miRNAs and 5 mRNAs involved in vascular pathology, inflammation and telomerase regulation. Significant positive correlations were present for 7 miRNAs with age, for 2 miRNAs with the MFS aortic root status (Z-score) and for 7 miRNAs with left ventricular end-diastolic diameter in MFS patients. In addition, miR-331-3p was significantly up-regulated in MFS patients without mitral valve prolapse (MVP) as compared with patients with MVP. CONCLUSIONS:Our data show deregulated gene and miRNA expression profiles in the peripheral blood of MFS patients, demonstrating several candidates for prognostic biomarkers for cardiovascular manifestations in MFS as well as targets for novel therapeutic approaches. A deregulation of miRNA expression seems to play an important role in MFS, highlighting the plethora of effects on post-transcriptional regulation of miRNAs and mRNAs initiated by constitutional mutations in single genes. Trial registration Nr: EA2/131/10 . Registered 28 December, 2010.
| S-EPMC5848586 | biostudies-literature
Project description:We performed integrated miRNA and mRNA expression profiling in blood samples of Marfan patients in order to investigate deregulated miRNA and mRNA networks in these patients which could serve as potential diagnostic and prognostic tools for MFS therapy.
2019-05-22 | GSE110965 | GEO
Project description:We performed integrated miRNA and mRNA expression profiling in blood samples of Marfan patients in order to investigate deregulated miRNA and mRNA networks in these patients which could serve as potential diagnostic and prognostic tools for MFS therapy.
2019-05-22 | GSE110964 | GEO
Project description:Deregulated MicroRNA and mRNA Expression Profiles in the Peripheral Blood of Patients with Marfan Syndrome (microRNA)
| PRJNA435421 | ENA
Project description:Deregulated MicroRNA and mRNA Expression Profiles in the Peripheral Blood of Patients with Marfan Syndrome (mRNA)
| PRJNA435419 | ENA
Project description:Deregulated MicroRNA and mRNA Expression Profiles in the Peripheral Blood of Patients with Marfan Syndrome
| PRJNA435416 | ENA
Project description:We analyzed miRNA and mRNA expression profiles in human peripheral blood lymphocytes (PBLs) incubated in microgravity condition, simulated by a ground-based rotating wall vessel (RWV) bioreactor. Our results show that 42 miRNAs were differentially expressed in MMG-incubated PBLs compared with 1 g incubated ones. Among these, miR-9-5p, miR-9-3p, miR-155-5p, miR-150-3p, and miR-378-3p were the most dysregulated. To improve the detection of functional miRNA-mRNA pairs, we performed gene expression profiles on the same samples assayed for miRNA profiling and we integrated miRNA and mRNA expression data. The functional classification of miRNA-correlated genes evidenced significant enrichment in the biological processes of immune/inflammatory response, signal transduction, regulation of response to stress, regulation of programmed cell death, and regulation of cell proliferation. We identified the correlation of miR-9-3p, miR-155-5p, miR-150-3p, and miR-378-3p expression with that of genes involved in immune/inflammatory response (e.g., IFNG and IL17F), apoptosis (e.g., PDCD4 and PTEN), and cell proliferation (e.g., NKX3-1 and GADD45A). Experimental assays of cell viability and apoptosis induction validated the results obtained by bioinformatics analyses demonstrating that in human PBLs the exposure to reduced gravitational force increases the frequency of apoptosis and decreases cell proliferation.
| S-EPMC4090438 | biostudies-literature
Project description:Pathogenic mutations in FBN1, encoding the glycoprotein, fibrillin-1, cause Marfan syndrome (MFS) and related connective tissue disorders. In the present study, qualitative and quantitative effects of 16 mutations, identified in FBN1 in MFS patients with systematically described phenotypes, were investigated in vitro.Qualitative analysis was performed with reverse transcription-PCR (RT-PCR) and gel electrophoresis, and quantitative analysis to determine the FBN1 mRNA levels in fibroblasts from the 16 patients with MFS was performed with real-time PCR.Qualitative analysis documented that the mutations c.4817-2delA and c.A4925G led to aberrant FBN1 mRNA splicing leading to in frame deletion of exon 39 and in exon 39, respectively. No difference in the mean FBN1 mRNA level was observed between the entire group of cases and controls, nor between the group of patients with missense mutations and controls. The mean expression levels associated with premature termination codon (PTC) and splice site mutations were significantly lower than the levels in patients with missense mutations. A high level of FBN1 mRNA in the patient with the missense mutation c.G2447T did not segregate with the mutation in three of his first degree relatives. No association was indicated between the FBN1 transcript level and specific phenotypic manifestations.Abnormal FBN1 transcripts were indicated in fibroblasts from patients with the splice site mutation c.4817-2delA and the missense mutation c.A4925G. While the mean FBN1 mRNA expression level in fibroblasts from patients with splice site and PTC mutations were lower than the mean level in patients with missense mutations and controls, inter-individual variability was high. The observation that high level of FBN1 mRNA in the patient with the missense mutation c.G2447T did not segregate with the mutation in the family suggests that variable expression of the normal FBN1 allele may contribute to explain the variability in FBN1 mRNA level.
| S-EPMC4683784 | biostudies-literature
Project description:The aim of this study was to elucidate the expression profile and the potential role of long non-coding RNA (LncRNA) in the peripheral blood mononuclear cells of primary Sjögren's syndrome (pSS) patients. RNA-seq technology was used to detect the differentially expressed LncRNAs and mRNAs between five age-and sex-matched paired pSS patients and healthy control PBMCs. The selected LncRNAs were detected in the validation study by RT-qPCR in 16 paired pSS patients and healthy controls. The GO, KEGG, co-localization, and co-expression analysis were performed to enrich the potential gene functions and pathways. In this study, 44 out of 1772 LncRNAs and 1034 out of 15,424 mRNAs were expressed differentially in the PBMCs of pSS patients. LINC00426, TPTEP1-202, CYTOR, NRIR, and BISPR were validated as aberrantly expressed, and these LncRNAs strongly correlated with disease activity of pSS. GO and KEGG pathway analysis revealed the significant enrichment of biological processes, cellular components, and molecular function of the up and down-regulated mRNAs, which were mainly concentrated in the immune response and immune system processes. Co-localization and co-expression analysis also revealed that differentially expressed LncRNAs in the PBMCs of pSS were strongly correlated to the mRNA functioning associated with immune response and cell metastasis. Numerous LncRNAs and mRNAs were found differentially expressed in the PBMCs of pSS patients, especially NRIR and BISPR; they interacted with the co-localized and co-expressed mRNAs, which might participate in the pathogenesis of pSS through the NF-κB, JAK-STAT, and other signaling pathways that regulate cell metastasis.
| S-EPMC7661519 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-12-31 | GSE54250 | GEO