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Discovery of extracellular vesicles derived miR-185-5p in patient’s plasma as an indicator for advanced adenoma and malignant tumor of colon

ABSTRACT: We attempted to screen and identify new plasma EV delivered microRNA can simultaneously diagnose AA, early CRC and advanced CRC in healthy people. We employed microRNA deep sequencing assay for the primary screen and performed TaqMan microRNA assay for further test and validation. Through stepwise screen and validation in two independent cohorts (cohort I: n=75, cohort II: n=104), we demonstrated that plasma EV-delivered miR-185-5p is a potential indicator of AA and CRC in Chinese patients. In the supplementary phase, we also preliminarily proved that miR-185-5p can promote the development of CRC in vivo and in vitro.

ORGANISM(S): Homo sapiens

PROVIDER: GSE220445 | GEO | 2023/09/11

REPOSITORIES: GEO

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Impaired AGO2/miR-185-3p/NRP1 Axis Promotes Colorectal Cancer Metastasis

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 | iProX

Expression data from Huh7.5 hepatoma cells transfected with 100 nM miR-185 mimic

Project description:Our work demonstrated that 25-hydroxycholesterol induces the expression of miR-185, a microRNA which reinforces the oxysterol's antiviral effects on hepatic metabolism. We used microarrays to detail the effect of miR-185 on hepatic gene expression, and, within repressed genes, identified an enrichment for genes associated with cholesterol biosynthesis.

2015-10-19 | GSE73165 | GEO

Deep sequencing identified serum extracellular vesicle delivered miR-181a-5p as an indicator for bone-metastatic prostate cancer (microarray)

Project description:Purpose: The goals of this study are to compare the serum extracellular vesicle (EV) delivered miRNA levels of patients with bone-metastatic prostate cancer (PCa), non-bone -metastatic PCa and benign prostatic hyperplasia (BPH), and to identify EV-delivered microRNAs in patient’s serum as indicators for bone-metastatic PCa. Methods:Serum extracellular vesicle delivered miRNA profiles of patients with bone-metastatic PCa or non-bone -metastatic PCa or BPH were generated by miRNA chip array, using Agilent-070156 Human_miRNA_V21.0_Microarray plateform. Results: Differential analysis showed the expressions of 27 EV delivered miRNAs were significantly different between serum of patients with bone-metastatic PCa and non-bone-metastatic PCa with a p value <0.05. the expressions of 5 EV delivered miRNAs were confirmed with qRT–PCR. Conclusions: Serum EV-delivered miR-181a-5p is a promising diagnostic biomarker for bone-metastatic PCa.

2020-01-31 | GSE134266 | GEO

Deep sequencing identified serum extracellular vesicle delivered miR-181a-5p as an indicator for bone-metastatic prostate cancer

Project description:Purpose: The goals of this study are to compare the serum extracellular vesicle (EV) delivered miRNA levels of patients with bone-metastatic prostate cancer (PCa), non-bone -metastatic PCa and benign prostatic hyperplasia (BPH), and to identify EV-delivered microRNAs in patient’s serum as indicators for bone-metastatic PCa. Methods:Serum extracellular vesicle delivered miRNA profiles of patients with bone-metastatic PCa or non-bone -metastatic PCa or BPH were generated by deep sequencing, using Illumina HiSeqTM 2500 platform Results: Using an optimized data analysis method, we mapped about 17 million sequence reads per sample. Differential analysis showed the expressions of 35 EV delivered miRNAs were significantly different between serum of patients with PCa and BPH, with a p value <0.05. the expressions of 5 EV delivered miRNAs were confirmed with qRT–PCR. Conclusions: Serum EV-delivered miR-181a-5p is a promising diagnostic biomarker for bone-metastatic PCa.

2020-01-31 | GSE134205 | GEO

MicroRNA-185 modulates CYP7A1 mediated bile acid metabolism through posttranscriptionally and posttranslationally regulation of FoxO1

Project description:Cholesterol 7alpha-hydroxylase (CYP7A1) is the rate limiting enzyme of bile acid biosynthetic pathway to convert cholesterol to bile acids, which is a major output pathway for cholesterol catabolism. In this study, we aimed to assess the potential regulatory mechanisms of microRNA-185 (miR-185) involved in cholesterol and bile acid homeostasis. This study provides convincing evidences about the critical role of miR-185 in FoxO1 modulation at both posttranscriptional and posttranslational levels, which account for the effects on CYP7A1 gene and its mediated cholesterol-bile acid metabolism. These results suggest an important role of miR-185 as a novel atherosclerosis-protective target for drug discovery.

2023-03-26 | GSE169693 | GEO

Mortierella sp. AD 185 isolate:AD 185

Project description:Mortierella sp. AD 185 Transcriptome - AD 185

| PRJNA582288 | ENA

Circulating miRNA sequencing in serum of patients with Cushing's syndrome and related controls

Project description:Cushing’s syndrome (CS) is a rare disease with high morbidity and mortality. Diagnosis and subtyping are complex and challenging. Circulating microRNAs were described to be useful as minimally invasive diagnostic markers. Our aim was to determine and compare the circulating microRNA expression profiles of patients with CS and controls. We included three groups of patients of the German Cushing’s registry: A.) patients with florid adrenal dependent CS scheduled for adrenalectomy (CPA); B.) patients with florid pituitary dependent CS scheduled for surgery (CD); and C.) patients in whom CS had been ruled out (controls). Next-generation sequencing was performed in the 30 CS serum samples before and after curative surgery, respectively, and in 10 baseline samples of controls. No significant differential expression was observed between all the CS samples and controls by NGS as well as by QPCR. The sequencing of the preoperative samples revealed a significant differential expression of miR-182-5p (p=0.02) between CD and controls. The differential expression was validated by QPCR in the discovery cohort and in an independent validation cohort. MiR-96-5p, miR-146b-5p, miR-183-5p, miR-185-5p, miR-616-5p and miR-629-5p were found to be significantly upregulated in CPA samples in comparison to CD group of the preoperative group in NGS. However, similar upregulation pattern could not be observed by QPCR in the discovery and validation cohorts. Additionally, miR-96-5p and miR-185-5p were found to be modulated by dexamethasone in controls. Thus, our study reports miR-182-5p as a possible biomarker for CD, which has to be validated in a prospective cohort.

2020-08-25 | GSE156693 | GEO

The miRNA expression characteristics in alopecia areata

Project description:To explore the regulatory effect between miRNAs and mRNAs and the possibility of miRNAs as specific blood-based biomarkers in the developmental process of severe alopecia areata (AA), human peripheral blood samples from AA patients and healthy donors were obtained for analysis. we identified 36 significantly differentially expressed miRNAs in severe active AA patients. MiRNA target gene prediction and functional annotation analysis showed a significant enrichment in several pathways including the ribosome, cancer, cell cycle, insulin signaling, TGF-β signaling and p53 signaling pathways. Analysis of the three kinds of network showed that miR-185-5p, miR-125b-5p, and miR-186-5p might play important and synergistic roles in the developmental process of AA. According to the receiver operating characteristic curve analysis, several miRNAs were selected for the quantitative real-time PCR validation and further applied as biomarkers to classify severe active AA patients and healthy individuals. Among the miRNAs, hsa-miR-210 and hsa-miR-1246 had high prediction with high accuracy.

2018-03-01 | GSE93978 | GEO

MicroRNA Profiling in Aplastic Anaemia (AA) Reveals Similarities between Secondary Myelodysplastic Syndromes (MDS) Arising from Clonal Progression and de novo MDS

Project description:Aplastic anaemia (AA) is a form of bone marrow failure (BMF) resulting in significant cytopenias and may progress with clonal evolution to myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). MicroRNA expression is dysregulated in MDS/AML but there are limited studies on its role in the pathogenesis of AA. Using stored BM samples (n=81) from 2006-2019 from 52 patients, we demonstrate key differences in miRNA expression between AA patients at diagnosis and de novo MDS patients (n=21). The five most significantly upregulated miRNA in MDS patients (downregulated in AA) were miR-130a-3p, miR-221-3p, miR-126-3p, miR-27b-3p and miR-196b-5p (adj p<0.001). However, at the time of AA clonal progression to secondary MDS/AML, no significant miRNA differences were identified suggesting that the underlying mechanistic pathways are similar between AA progression to MDS/AML and de novo MDS. At diagnosis, miR-127-3p, miR-1271-5p, miR-301b-5p, miR-3934-5p and miR-4531 (adj p=0.081) were upregulated in those whose AA eventually progressed in comparison to those without eventual clonal progression. Using KEGG pathway analysis derived from miRPathDBv2.0, cytokine-cytokine receptor interaction, TGF-, MAP kinase, prolactin, Hippo, neurotrophin and FOXO signalling pathways were enriched in AA patients with clonal progression to MDS/AML; these pathways were similarly enriched in the de novo MDS cohort. These studies highlight the differing miRNA expression profiles in AA and MDS and in AA clonal evolution to MDS/AML.

2023-09-02 | GSE242216 | GEO

Small RNA-sequencing in primary breast fibroblasts treated and not-treated with breast cancer exosomes

Project description:We report the application of small-RNA-sequencing technology for high-throughput profiling of microRNAs in primary mammalian fibroblasts upon breast cancer-derived exosome treatment. We generated microRNA expression profile by obtaining 928(?) microRNA sequences diffrentially expressed between fibroblasts incubated with exosomes and with PBS (NT,negative control). Among 14 (?) microRNAs significantly upregulated in primary fibroblasts after exosome treatment, we demonstrated that microRNA-185-5p, microRNA-652-5p, and microRNA-1246 were actively involved in fibroblasts functional activation, thus corroborating our initial hypothesis.

2022-03-02 | GSE185654 | GEO

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