Serum miRNA-186-3P and miRNA-186-3P constitute a novel diagnostic signature for palindromic rheumatism
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PROVIDER: PRJNA1218265 | ENA |
REPOSITORIES: ENA
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Project description:Background: Palindromic rheumatism (PR) is a unique disease characterized by the intermittent inflammation of different joints that may progress to a variety of immune-related diseases. Unclear diagnostic criteria have limited the research on its pathogenesis and treatment options. Recently, microRNAs (miRNAs) have been used in the diagnosis of various diseases; however, the role of miRNAs in PR diagnosis remains unexplored. Using next-generation high-throughput sequencing (NGS), this study aimed to screen miRNAs specifically expressed in the serum of patients with PR to construct a diagnostic signature and verify its diagnostic efficacy. Methods: Patients with PR (N=4), patients with rheumatoid arthritis (RA; N=3), and healthy controls (N=3) were included in an exploration cohort. Differentially expressed miRNAs were screened using NGS to construct diagnostic signatures and bioinformatics tools were used to perform target gene enrichment analysis of the top 25 differentially expressed miRNAs, both upregulated and downregulated. RT-qPCR was used to verify the differential expression of the diagnostic signatures in the three validation cohorts of patients with PR (N=27) and RA (N=30), and healthy controls (N=31), and the diagnostic efficiency of the diagnostic signatures was evaluated using receiver operator characteristic (ROC) curves. Results: A total of 130 differentially expressed miRNAs–35 upregulated and 95 downregulated miRNAs–were found in the PR exploration cohort, which differed between both RA and healthy controls. miRNA-186-3p showed the largest upregulated difference, and miRNA-382-3p showed the largest downregulated difference, and consequently, were selected to construct the diagnostic signature. In the ROC analysis of the validation cohort, the diagnostic signature produced an area under the ROC curve (AUC) of 1 (95% CI 1.000-1.000) compared with healthy controls. For patients with RA, the diagnostic signature produced an AUC of 0.915 (95% CI 0.842-0.988). However, miRNA-186-3p and miRNA-382-3p levels were not associated with disease activity in patients with PR. Conclusion: A diagnostic signature comprising miRNA-186-3p and miRNA-382-3p can effectively diagnose and differentiate PR from RA. This study provides a basis for the creation of a clinical miRNA signature for the diagnosis of PR.
2025-02-02 | GSE288542 | GEO
Project description:Increasing evidence suggests that global downregulation of miRNA expression is a hallmark of human cancer, potentially due to defects in the miRNA processing machinery. In this study, we found that the protein expression of Argonaute 2 (AGO2), a key regulator of miRNA processing, was downregulated in colorectal cancer (CRC) tissues, which was also consistent with the findings of the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Furthermore, the correlation between the levels of AGO2 and epithelial-mesenchymal transition (EMT) markers (E-cadherin and vimentin) indicated that reduced levels of AGO2 promoted EMT in CRC. Low expression of AGO2 was an indicator of a poor prognosis among CRC patients. Knockdown of AGO2 in CRC cells promoted migration, invasion and metastasis formation in vitro and in vivo but had no influence on proliferation. To provide detailed insight into the regulatory roles of AGO2, we performed integrated transcriptomic, quantitative proteomic and microRNA sequencing (miRNA-seq) analyses of AGO2 knockdown cells and the corresponding wild-type cells and identified neuropilin 1 (NRP1) as a new substrate of AGO2 via miR-185-3p. Our data provided evidence that knockdown of AGO2 resulted in a reduction of miR-185-3p expression, leading to the upregulation of the expression of NRP1, which is a direct target of miR-185-3p, and elevated CRC cell metastatic capacity. Inhibition of NRP1 or treatment with a miR-185-3p mimic successfully rescued the phenotypes of impaired AGO2, which suggested that therapeutically targeting the AGO2/miR-185-3p/NRP1 axis may be a potential treatment approach for CRC.
2021-02-11 | PXD024171 |
Project description:NTP4 modulates miRNA accumulation via asymmetric modification of miRNA-3p/5p duplex
| PRJNA634468 | ENA
Project description:Dysregulated miRNA expression contributes to development of arsenic-induced cutaneous squamous cell carcinoma (cSCC). hsa-miR-186 (called “miR-186” henceforth) is overexpressed in arsenical cSCC tissues as well as in preclinical cell line model of arsenical cSCC. Simultaneous miR-186 overexpression and chronic inorganic trivalent arsenite (iAs; 100 nM) exposure transformed human HaCaT cell line preferentially over miR-186 exposure or iAs exposure alone. Both iAs and miR-186 regulate the expression of wide range of mRNA targets. However, how their interaction impact the transcriptome-wide mRNA expression landscape ushering in cancer is unknown. We performed longitudinal RNA-seq analysis in passage-matched HaCaT cells clones (±miR-186 overexpression) with simultaneous chronic iAs exposure (0/100 nM; 29 weeks) at 12 and 29 weeks. We determined the impact of each factor and their interaction towards differential gene expression and pathways dysregulation employing to different statistical approaches (t-statistic and 2-factor ANOVA). We show that a core set of pathways are dysregulated deterministically irrespective of the statistical approach chosen, possibly representing necessary changes for transformation. Our data suggests that each clonal line could take unique routes to dysregulate these core set of pathways necessary for transformation, highlighting the possible role of stochasticity in cancer development. We provide evidence to sift the strengths of weaknesses of each statistical methodology in providing biological understanding of events that play crucial role in carcinogenesis in large datasets with multiple contributing variables.
2025-01-23 | GSE276586 | GEO
Project description:Severe acute respiratory syndrome coronavirus (SARS-CoV) and the closely related SARS-CoV-2 are emergent highly pathogenic human respiratory viruses causing acute lethal disease associated with lung damage and dysregulated inflammatory responses. SARS-CoV envelope protein (E) is a virulence factor involved in the activation of various inflammatory pathways. Here, we study the contribution of host miRNAs to the virulence mediated by E protein. Small RNAseq analysis of infected mouse lungs identified miRNA-223 as a potential regulator of pulmonary inflammation, since it was significantly increased in SARS-CoV-WT virulent infection as compared to the attenuated SARS-CoV-∆E infection. In vivo inhibition of miRNA-223-3p increased mRNA levels of pro-inflammatory cytokines and NLRP3 inflammasome, suggesting that during lung infection, miRNA-223 might contribute to restrict an excessive inflammatory response. Interestingly, miRNA-223-3p inhibition also increased the levels of the CFTR transporter, which is involved in edema resolution and was significantly downregulated in the lungs of mice infected with the virulent SARS-CoV-WT virus. At the histopathological level, a decrease in the pulmonary edema was observed when miR-223-3p was inhibited, suggesting that miRNA-223-3p was involved in the regulation of the SARS-CoV-induced inflammatory pathology. These results indicate that miRNA-223 participates in the regulation of E protein mediated- inflammatory response during SARS-CoV infection by targeting different host mRNAs involved in the pulmonary inflammation and identify miRNA-223 as a potential therapeutic target in SARS-CoV infection.
2022-02-04 | GSE180563 | GEO
Project description:Colorectal cancer is a prevalent disease that is the third most common cause of cancer-associated death globally. The genetic mechanisms underlying tumor aggressiveness in colorectal cancer require further elucidation. Taking advantage of a large panel of human metastatic colorectal cancer xenografts and matched stem-like cell cultures (m-colospheres), we show here that overexpression of miRNA-483-3p, encoded by a frequently amplified gene locus encompassing IGF2, confers an aggressive phenotype. Following ectopic overexpression of miRNA-483-3p, m-colospheres displayed (i) increased proliferative response to exogenous EGFR family ligands EGF and neuregulin 1; (ii) increased spontaneous and growth factor-induced invasiveness and epithelial-mesenchymal transition (EMT); and (iii) enhanced stem-cell frequency and resistance to differentiation. Transcriptomic analyses and functional validation found that miRNA-483-3p directly targets NDRG1, a known metastasis suppressor responsible for downregulation of the EGFR family. As a result, induced or endogenous miRNA-483-3p overexpression associated with stimulation of the signaling pathway triggered by ERBB3, including AKT and GSK3β, which is responsible for EMT transcription factor activation. Consistently, treatment of miRNA-483-3p-overexpressing m-colospheres with selective ERBB3 antibodies counteracted their proliferative and invasive phenotype. The pro-malignant role of miRNA-483-3p was further corroborated by analysis of human colorectal tumors, where miRNA-483-3p expression levels directly correlated with expression of EMT transcription factors and poor prognosis, and downregulation of miRNA-483-3p, which prevented invasion of tumors formed by m-colosphere transplantation. These results unveil a previously unrecognized link between miRNA-483-3p, NDRG1, and ERBB3-AKT signaling, which can directly support colorectal cancer invasion and is amenable to therapeutic targeting.
2023-03-13 | GSE209535 | GEO
Project description:Background: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disorder, characterized by cardiomyocyte hypertrophy, cardiomyocyte disarray and fibrosis, which has a prevalence of ~1:200-500 and predisposes individuals to sudden death and heart failure. The mechanisms through which diverse HCM-causing mutations cause cardiac dysfunction remain mostly unknown and their identification may reveal new therapeutic avenues. MicroRNAs have emerged as critical regulators of gene expression and disease phenotype in various pathologies. We explored whether miRNAs could play a role in HCM pathogenesis and offer potential therapeutic targets. Methods and Results: Using high-throughput miRNA expression profiling and qPCR analysis in two distinct mouse models of HCM, we found that miR-199a-3p expression levels are upregulated in mutant mice compared to age- and treatment-matched wild-type mice. We also found that miR-199a-3p expression is enriched in cardiac non-myocytes compared to cardiomyocytes. When we expressed miR-199a-3p mimic in cultured primary cardiac non-myocytes and analyzed the conditioned media by proteomics, we found that several ECM proteins (e.g., TSP2, FBLN3, COL11A1, LYOX) were differentially expressed. We confirmed our proteomics findings by qPCR analysis of selected mRNAs and demonstrated that miR-199a-3p mimic expression in cardiac non-myocytes drives upregulation of ECM genes including Tsp2, Fbln3, Pcoc1, Col1a1 and Col3a1. To examine the role of miR-199a-3p in vivo, we inhibited its function using lock-nucleic acid (LNA)-based inhibitors (antimiR-199a-3p) in an HCM mouse model. Our results revealed that progression of cardiac fibrosis is attenuated when miR-199a-3p function is inhibited in mild-to-moderate HCM. Finally, guided by computational target prediction algorithms, we identified mRNAs Cd151 and Itga3 as direct targets of miR-199a-3p and have shown that miR-199a-3p mimic expression negatively regulates AKT activation in cardiac non-myocytes. Conclusions: Altogether, our results suggest that miR-199a-3p may contribute to cardiac fibrosis in HCM through its actions in cardiac non-myocytes. Thus, inhibition of miR-199a-3p in mild-to-moderate HCM may offer therapeutic benefit in combination with complementary approaches that target the primary defect in cardiac myocytes.
2024-01-26 | PXD042904 | Pride
Project description:Methanobrevibacter smithii CAG:186 overview
| PRJNA207153 | ENA
Project description:To clarify the role of miR-186 in GIST, we carried out a gene expression microarray analysis using GIST-T1 cells transfected with a miR-186 inhibitor or a negative control. We found that 253 probe sets (229 unique genes) were upregulated (>1.5-fold) by inhibition of miR-186 in GIST-T1 cells.
2017-01-01 | GSE85613 | GEO
Project description:Massilia aurea strain:186 Genome sequencing
| PRJNA1135903 | ENA