Extracellular vesicles miR-574-5p and miR-181a-5p as prognostic markers in NSCLC patients treated with nivolumab
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PROVIDER: PRJNA856872 | ENA |
REPOSITORIES: ENA
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Project description:Plasma from 245 patients with advanced NSCLC who received nivolumab as second-line therapy was collected and analyzed. EV-miRnome was profiled on 174/245 patients by microarray platform and selected EV-miRs were validated by qPCR. A prognostic model combining EV-miR and clinical variables was built using stepwise Cox regression analysis and tested on an independent patient cohort (71/245). EV-PD-L1 gene copy number was assessed by digital PCR. For 54 patients with disease control, EV-miR changes at best response versus baseline were investigated by microarray and validated by qPCR. EV-miRNome profiling at baseline identified two EV-miR (miR-181a-5p, miR-574-5p) that, combined with performance status, are capable of discriminating patients unlikely from those that are likely to benefit from immunotherapy (median overall survival of 4 months or higher than 9 months, respectively). EV-PD-L1 digital evaluation reported higher baseline copy number in patients at increased mortality risk, without improving the prognostic score. Best response EV-miRNome profiling selected six deregulated EV-miRs (miR19a-3p, miR-20a-5p, miR-142-3p, miR-1260a, miR-1260b, miR-5100) in responding patients. Their longitudinal monitoring highlighted a significant downmodulation already in the first treatment cycles, which lasted more than six months. Grantee: Simona Coco Grantor: Italian Ministry of Health Grant ID: CO-2016-02361470 Grant Title: Exosomal miRNA signature as prognostic marker in advanced non-small cell lung cancer (NSCLC) patients treated with Nivolumab
2024-07-28 | GSE207715 | GEO
Project description:We aimed to characterize decoy to the RNA-binding protein CUG-RNA binding protein 1 (CUGBP1 mechanism in A549 lung cancer cells. We identified several new canonical targets of CUGBP1 but those were not regulated by miR-574-5p via the decoy mechanism. This can be explained by the localization of CUGBP1 and miR-574-5p in the nucleus, where CUGBP1 regulates alternative splicing. Next, we analyzed the 3’UTRs of potential targets and found that the decoy-dependent regulation of mPGES-1 splicing is unique. Therefore, we postulate that in A549 cells mPGES-1 is the only protein regulated by the decoy mechanism of CUGBP1 and miR-574-5p which suggests that the decoy mechanism allows the specific regulation of the expression of distinct targets.
2020-03-02 | PXD016803 | Pride
Project description:RNA profiling by RNA-Seq analyses showed that in comparison with the control Dotap-treated cells, miR-574-5p transfection for 24 h resulted in significant up-regulation of 277 genes and down-regulation of 80 genes by at least 2-fold in the miR-574-5p-transfected splenocytes. Gene ontology and pathway enrichment analyses showed that the 277 significantly up-regulated genes in miR-574-5p-transfected cells were highly enriched and clustered in pathways associated with interferon and cytokine signaling, antiviral mechanisms, translesion synthesis and autoimmunity .
2023-07-04 | GSE236337 | GEO
Project description:Background: Oral squamous cell carcinoma (OSCC) is a common malignant tumor associated with poor prognosis. MicroRNAs (miRNAs) play crucial regulatory roles in the cancer development. However, the role of miRNAs in OSCC development and progression is not well understood. Methods: We sought to establish a dynamic Chinese hamster OSCC animal model, construct miRNA differential expression profiles of its occurrence and development, predict its targets, and perform functional analysis and validation in vitro. Results: Using expression and functional analyses, the key candidate miRNA (miR-181a-5p) was selected for further functional research, and the expression of miR-181a-5p in OSCC tissues and cell lines was detected. Subsequently, transfection technology and a nude mouse tumorigenic model were used to explore potential molecular mechanisms. miR-181a-5p was significantly downregulated in human OSCC specimens and cell lines, and decreased miR-181a-5p expression was observed in multiple stages of the Chinese hamster OSCC animal model. Moreover, upregulated miR-181a-5p significantly inhibited OSCC cell proliferation, colony formation, invasion, and migration; blocked the cell cycle; and promoted apoptosis. BCL2 was identified as a target of miR-181a-5p. BCL2 may interact with apoptosis- (BAX), invasion- and migration- (TIMP1, MMP2, and MMP9), and cell cycle-related genes (KI67, E2F1, CYCLIND1, and CDK6) to further regulate biological behavior. Tumor xenograft analysis indicated that tumor growth was significantly inhibited in the high miR-181a-5p expression group. Conclusions: Our findings indicate that miR-181a-5p can be used as a potential biomarker and provide a novel animal model for mechanistic research on oral cancer.
2023-01-10 | GSE222429 | GEO
Project description:To profile gene expression in human HeLa cells follwing the knockdown of miR-574-5p, as compared to control HeLa cells Gene ontology and clustering analyses revealed that the differentially-expressed genes were highly enriched for the immune system and its related signal transduction pathways.
2023-07-04 | GSE235926 | GEO
Project description:Purpose: FOLFIRINOX has become standard therapy for patients with advanced stages pancreatic ductal adenocarcinoma (PDAC). However, only a subset of patients benefits from this therapy and biomarkers to guide clinical decisions are lacking. This study aimed to discover circulating microRNAs (miRNAs) as potential stratifying and monitoring biomarkers in patients with PDAC treated with FOLFIRINOX and to investigate their functional roles. Methods: A microarray was used in plasma samples from a first cohort of 11 patients selected based on their long versus short progression-free survival (PFS) after FOLFIRINOX. Nine miRNAs were validated using RT-qPCR in an independent cohort (n=43). The best discriminative miRNA was evaluated in tumor tissue samples and associated with clinicopathological features by Cox regression analyses. In vitro studies explored its role on cell proliferation, key downstream targets, and interaction with 5-fluorouracil, irinotecan, and oxaliplatin. Results: MiR-181a-5p was validated as significantly down-regulated in non-progressive compared to progressive patients after FOLFIRINOX. In multivariate analysis, this down-regulation correlated with improved PFS and overall survival, especially combined with CA19.9 decline (log-rank p<0.001, HR=0.153, 95% C.I. 0.067–0.347 and log-rank p=0.033, HR=0.201, 95% C.I. 0.070–0.576, respectively). Overexpression of miR-181a-5p increased proliferation of PDAC cells and inversely correlated with expression of ATM. Furthermore, inhibition of miR-181a-5p coupled with oxaliplatin exposure increased DNA damage and decreased cell viability. Conclusion: Our findings endorse miR-181a-5p as a biomarker for monitoring response to FOLFIRINOX and prognostication. MiR-181a-5p inhibition can potentially enhance sensitivity to oxaliplatin by amplifying the DNA damage response and cell death.
2019-01-01 | GSE109647 | GEO
Project description:Purpose: The target mRNAs of miR-574 in mouse heart are unknown. The goal of this study is to use next generation sequencing (NGS) RNA-seq followed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) methods to identify the downstream target genes that are directly regulated by miR-574 in murine hearts at the mRNA level. Results: Using a well established data analysis workflow from the Genomic Research Center from University of Rochester Medical Center, we analyzed RNA-seq data. We have identified novel genes that are regulated by miR-574 via miRNA-induced silencing complex (miRISC). We defined differentially regulated genes (either upregulated or downregulated) with statistical significance in total RNA expression change (p value <0.05 for differential expressed genes). We identified 34 upregulated genes involved in the small molecule metabolism and the mitochondrial function, and 49 downregulated genes in the electron transport chain (ETC) complex, oxidative phosphorylation, and tricarboxylic acid cycle. Conclusions: Among 34 upregulated genes, eight genes contain the predicted target seed sequence of miR-574-5p and Fam210a (family with sequence similarity 210 member A) is the only upregulated gene that contains the target seed sequence of both the guide strand miR-574-5p and the passenger strand miR-574-3p. We confirmed that FAM210A was the downstream target of both miR-574-5p and miR-574-3p in vivo and in vitro. Based on our results, we conclude that miR-574 downregulates a limited number of mitochondrial function related genes including FAM210A in mouse hearts at baseline.
2020-04-23 | GSE149168 | GEO
Project description:RNA-Seq analyses in miR-574-5p-transfected mouse splenocytes
| PRJNA990654 | ENA
Project description:This is a prospective-retrospective study to determine if the expression of the miRNA’s miR-31-3p and miR-31-5p are prognostic of patient outcomes or predictive of the benefit from anti-EGFR therapy in stage III Colon Cancer. The present study will utilize FFPE tumor samples collected from patients enrolled in the PETACC-8 study conducted by the Fédération Francophone de Cancérologie Digestive (FFCD). This phase 3 clinical trial prospectively randomized fully resected stage III colon cancer patients to receive adjuvant treatment with either FOLFOX-4 plus cetuximab or FLOFOX-4 alone.
| 2260465 | ecrin-mdr-crc
Project description:MiRNAs have been shown to alter both protein expression and secretion in different cellular contexts. By combining in vitro, in vivo and in silico techniques, we demonstrated that overexpression of pre-miR-1307 reduced the ability of breast cancer cells to induce endothelial cell sprouting and angiogenesis. However, the molecular mechanism behind this and the effect of the individual mature miRNAs derived from pre-miR-1307 on protein secretion and is largely unknown. Here, we overexpressed miR-1307-3p|0, -3p|1 and 5p|0 in MDA-MB-231 breast cancer cells and assessed the impact of miRNA overexpression on protein secretion by Mass Spectrometry. Unsupervised hierarchical clustering revealed a distinct phenotype induced by overexpression of miR-1307-5p|0 compared to the controls and to the 5’isomiRs derived from the 3p-arm. Together, our results suggest different impacts of miR-1307-3p and miR-1307-5p on protein secretion which is in line with our in vitro observation that miR-1307-5p, but not the isomiRs derived from the 3p-arm reduce endothelial cell sprouting in vitro. Hence these data support the hypothesis that miR-1307-5p is at least partly responsible for impaired vasculature in tumors overexpressing pre-miR-1307.
2024-12-11 | PXD041087 | Pride