Circulating Exosomal miR-20b-5p is Elevated in Type 2 Diabetes and Could Impair Insulin Action in Human Skeletal Muscle.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE102295 | GEO | 2019/01/10
REPOSITORIES: GEO
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Project description:The microRNA (miRNA) expression profile of plasma exosome in pregnant women complicated with gestational diabetes mellitus (GDM) has not been fully clarified. In this study, differentially expressed miRNAs in plasma exosomes were identified by high-throughput small RNA sequencing in 12 GDM and 12 normal glucose tolerance (NGT) pregnant women and validated in 102 GDM and 101 NGT pregnant women. A total of 22 exosomal miRNAs were found and five of them were verified by qRT-PCR. Exosomal miR-423-5p was upregulated, while miR-99a-5p, miR-192-5p, miR-148a-3p, and miR-122-5p were downregulated in pregnant women complicated with GDM.
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Project description:The contribution of microRNA-mediated posttranscriptional regulation on the final proteome in differentiating cells remains elusive. Here, we evaluated the impact of microRNAs (miRNAs) on the proteome of human umbilical cord blood-derived unrestricted somatic stem cells (USSC) during retinoic acid (RA) differentiation by a systemic approach using next generation sequencing analysing mRNA and miRNA expression and quantitative mass spectrometry-based proteome analyses. Interestingly, regulation of mRNAs and their dedicated proteins highly correlated during RA-incubation. Additionally, RA-induced USSC demonstrated a clear separation from native USSC thereby shifting from a proliferating to a metabolic phenotype. Bioinformatic integration of up- and downregulated miRNAs and proteins initially implied a strong impact of the miRNome on the XXL-USSC proteome. However, quantitative proteome analysis of the miRNA contribution on the final proteome after ectopic overexpression of downregulated miR-27a-5p and miR-221-5p or inhibition of upregulated miR-34a-5p, respectively, followed by RA-induction revealed only minor proportions of differentially abundant proteins. In addition, only small overlaps of these regulated proteins with inversely abundant proteins in non-transfected RA-treated USSC were observed. Hence, mRNA transcription rather than miRNA-mediated regulation is the driving force for protein regulation upon RA-incubation, strongly suggesting that miRNAs are fine-tuning regulators rather than active primary switches during RA-induction of USSC.
2020-01-31 | PXD016915 | Pride
Project description:Patients with diabetes mellitus (DM) have an epidemiologically higher risk for hepatocellular carcinoma (HCC). In mouse models, administration of streptozotocin (STZ) induces insulin-dependent DM by causing islet beta-cell dysfunction and also induced hepatocellular carcinoma (HCC) after 12 weeks. We attempted to elucidate the carcinogenic mechanism in the precancerous state by using hepatic miRNAs and create precancerous marker using exosomal miRNA. Serum and liver tissues were collected from STZ mice and non-treated mice (CTL mice) at 6, 10 and 12W. Total RNA in liver and exosome were extracted. Histological examination in liver in HE stain and hepatic and exosomal miRNA analysis were serially performed. miRNA and mRNA was analyzed by next-generation sequencing (NGS). The raw data of NGS was analyzed by Principal Component analysis. No inflammation or fibrosis was found in the liver in CTL mice during the observation period. In STZ-treated mice, regeneration and inflammation of hepatocytes was found at 6W and then nodules of atypical hepatocytes were found at 10 and 12 W. Expression of let-7f-5p, miR-21a-5p, 22-3p, and 26a-5p in liver of STZ mice was significantly increased during 6-10W, and these miRNAs controlled several tumor suppressor genes as target genes. We also identified six novel miRNAs associated with precancerous status. Furthermore, miR-122-5p and miR-192-5p in exosome were significantly upregulated in STZ mice in precancerous state. The expression of miRNAs that regulate tumor suppressor genes was enhanced even before carcinogenesis, and the expression of these miRNAs was not affected by liver fibrosis. In addition, the expression pattern of miRNAs in exosome is expected to be a marker for predicting carcinogenesis. Patients with diabetes mellitus (DM) have an epidemiologically higher risk for hepatocellular carcinoma (HCC). In mouse models, administration of streptozotocin (STZ) induces insulin-dependent DM by causing islet beta-cell dysfunction and also induced hepatocellular carcinoma (HCC) after 12 weeks. We attempted to elucidate the carcinogenic mechanism in the precancerous state by using hepatic miRNAs and create precancerous marker using exosomal miRNA. Serum and liver tissues were collected from STZ mice and non-treated mice (CTL mice) at 6, 10 and 12W. Total RNA in liver and exosome were extracted. Histological examination in liver in HE stain and hepatic and exosomal miRNA analysis were serially performed. miRNA and mRNA was analyzed by next-generation sequencing (NGS). The raw data of NGS was analyzed by Principal Component analysis. No inflammation or fibrosis was found in the liver in CTL mice during the observation period. In STZ-treated mice, regeneration and inflammation of hepatocytes was found at 6W and then nodules of atypical hepatocytes were found at 10 and 12 W. Expression of let-7f-5p, miR-21a-5p, 22-3p, and 26a-5p in liver of STZ mice was significantly increased during 6-10W, and these miRNAs controlled several tumor suppressor genes as target genes. We also identified six novel miRNAs associated with precancerous status. Furthermore, miR-122-5p and miR-192-5p in exosome were significantly upregulated in STZ mice in precancerous state. The expression of miRNAs that regulate tumor suppressor genes was enhanced even before carcinogenesis, and the expression of these miRNAs was not affected by liver fibrosis. In addition, the expression pattern of miRNAs in exosome is expected to be a marker for predicting carcinogenesis. Patients with diabetes mellitus (DM) have an epidemiologically higher risk for hepatocellular carcinoma (HCC). In mouse models, administration of streptozotocin (STZ) induces insulin-dependent DM by causing islet beta-cell dysfunction and also induced hepatocellular carcinoma (HCC) after 12 weeks. We attempted to elucidate the carcinogenic mechanism in the precancerous state by using hepatic miRNAs and create precancerous marker using exosomal miRNA. Serum and liver tissues were collected from STZ mice and non-treated mice (CTL mice) at 6, 10 and 12W. Total RNA in liver and exosome were extracted. Histological examination in liver in HE stain and hepatic and exosomal miRNA analysis were serially performed. miRNA and mRNA was analyzed by next-generation sequencing (NGS). The raw data of NGS was analyzed by Principal Component analysis. No inflammation or fibrosis was found in the liver in CTL mice during the observation period. In STZ-treated mice, regeneration and inflammation of hepatocytes was found at 6W and then nodules of atypical hepatocytes were found at 10 and 12 W. Expression of let-7f-5p, miR-21a-5p, 22-3p, and 26a-5p in liver of STZ mice was significantly increased during 6-10W, and these miRNAs controlled several tumor suppressor genes as target genes. We also identified six novel miRNAs associated with precancerous status. Furthermore, miR-122-5p and miR-192-5p in exosome were significantly upregulated in STZ mice in precancerous state. The expression of miRNAs that regulate tumor suppressor genes was enhanced even before carcinogenesis, and the expression of these miRNAs was not affected by liver fibrosis. In addition, the expression pattern of miRNAs in exosome is expected to be a marker for predicting carcinogenesis.
2020-12-22 | GSE153581 | GEO
Project description:Patients with diabetes mellitus (DM) have an epidemiologically higher risk for hepatocellular carcinoma (HCC). In mouse models, administration of streptozotocin (STZ) induces insulin-dependent DM by causing islet beta-cell dysfunction and also induced hepatocellular carcinoma (HCC) after 12 weeks. We attempted to elucidate the carcinogenic mechanism in the precancerous state by using hepatic miRNAs and create precancerous marker using exosomal miRNA. Serum and liver tissues were collected from STZ mice and non-treated mice (CTL mice) at 6, 10 and 12W. Total RNA in liver and exosome were extracted. Histological examination in liver in HE stain and hepatic and exosomal miRNA analysis were serially performed. miRNA and mRNA was analyzed by next-generation sequencing (NGS). The raw data of NGS was analyzed by Principal Component analysis. No inflammation or fibrosis was found in the liver in CTL mice during the observation period. In STZ-treated mice, regeneration and inflammation of hepatocytes was found at 6W and then nodules of atypical hepatocytes were found at 10 and 12 W. Expression of let-7f-5p, miR-21a-5p, 22-3p, and 26a-5p in liver of STZ mice was significantly increased during 6-10W, and these miRNAs controlled several tumor suppressor genes as target genes. We also identified six novel miRNAs associated with precancerous status. Furthermore, miR-122-5p and miR-192-5p in exosome were significantly upregulated in STZ mice in precancerous state. The expression of miRNAs that regulate tumor suppressor genes was enhanced even before carcinogenesis, and the expression of these miRNAs was not affected by liver fibrosis. In addition, the expression pattern of miRNAs in exosome is expected to be a marker for predicting carcinogenesis. Patients with diabetes mellitus (DM) have an epidemiologically higher risk for hepatocellular carcinoma (HCC). In mouse models, administration of streptozotocin (STZ) induces insulin-dependent DM by causing islet beta-cell dysfunction and also induced hepatocellular carcinoma (HCC) after 12 weeks. We attempted to elucidate the carcinogenic mechanism in the precancerous state by using hepatic miRNAs and create precancerous marker using exosomal miRNA. Serum and liver tissues were collected from STZ mice and non-treated mice (CTL mice) at 6, 10 and 12W. Total RNA in liver and exosome were extracted. Histological examination in liver in HE stain and hepatic and exosomal miRNA analysis were serially performed. miRNA and mRNA was analyzed by next-generation sequencing (NGS). The raw data of NGS was analyzed by Principal Component analysis. No inflammation or fibrosis was found in the liver in CTL mice during the observation period. In STZ-treated mice, regeneration and inflammation of hepatocytes was found at 6W and then nodules of atypical hepatocytes were found at 10 and 12 W. Expression of let-7f-5p, miR-21a-5p, 22-3p, and 26a-5p in liver of STZ mice was significantly increased during 6-10W, and these miRNAs controlled several tumor suppressor genes as target genes. We also identified six novel miRNAs associated with precancerous status. Furthermore, miR-122-5p and miR-192-5p in exosome were significantly upregulated in STZ mice in precancerous state. The expression of miRNAs that regulate tumor suppressor genes was enhanced even before carcinogenesis, and the expression of these miRNAs was not affected by liver fibrosis. In addition, the expression pattern of miRNAs in exosome is expected to be a marker for predicting carcinogenesis. Patients with diabetes mellitus (DM) have an epidemiologically higher risk for hepatocellular carcinoma (HCC). In mouse models, administration of streptozotocin (STZ) induces insulin-dependent DM by causing islet beta-cell dysfunction and also induced hepatocellular carcinoma (HCC) after 12 weeks. We attempted to elucidate the carcinogenic mechanism in the precancerous state by using hepatic miRNAs and create precancerous marker using exosomal miRNA. Serum and liver tissues were collected from STZ mice and non-treated mice (CTL mice) at 6, 10 and 12W. Total RNA in liver and exosome were extracted. Histological examination in liver in HE stain and hepatic and exosomal miRNA analysis were serially performed. miRNA and mRNA was analyzed by next-generation sequencing (NGS). The raw data of NGS was analyzed by Principal Component analysis. No inflammation or fibrosis was found in the liver in CTL mice during the observation period. In STZ-treated mice, regeneration and inflammation of hepatocytes was found at 6W and then nodules of atypical hepatocytes were found at 10 and 12 W. Expression of let-7f-5p, miR-21a-5p, 22-3p, and 26a-5p in liver of STZ mice was significantly increased during 6-10W, and these miRNAs controlled several tumor suppressor genes as target genes. We also identified six novel miRNAs associated with precancerous status. Furthermore, miR-122-5p and miR-192-5p in exosome were significantly upregulated in STZ mice in precancerous state. The expression of miRNAs that regulate tumor suppressor genes was enhanced even before carcinogenesis, and the expression of these miRNAs was not affected by liver fibrosis. In addition, the expression pattern of miRNAs in exosome is expected to be a marker for predicting carcinogenesis.
2020-12-22 | GSE153580 | GEO
Project description:Milk microRNAs (miRNAs) encapsulated in extracellular vesicles (EVs) are a novel class of bioactive food compounds. Milk produced by cows with subclinical mastitis threatens animals healthy and milk safety. However, little is known about the differentially expressed miRNA in milk-derived EVs related to subclinical mastitis. This study profiled miRNAs in milk-derived EVs from healthy cows and cows with subclinical mastitis. The potential targets for differentially expressed (DE) miRNAs were predicted. Milk-derived EVs were isolated from healthy cows (n = 7, the control group) and cows with subclinical (n = 7, the SM group). Two hundred ninety miRNAs (221 known and 69 novel ones) were identified. The top 20 miRNAs were commonly abundant (> 0.1% of the total read counts) in Healthy and SM groups, were regarded as abundant bovine milk-derived EVs miRNAs. MiR-21-5p was the most highly expressed known miRNA. Target genes of the top 20 abundant miRNAs were significantly enriched in Ras signaling pathway. The bta-miR-21-5p, bta-miR-30a-5p and miR-6-1096 were differentially expressed. For DE miRNAs, there was no significantly enriched pathways were found in the KEGG enrichment analysis. The linkage between the validated target genes and diseases suggested that we pay particular attention to exosome miRNAs from mastitic milk in milk safety.
2022-08-31 | GSE201588 | GEO
Project description:This study aimed to investigate the molecular mechanism responsible for primary open-angle glaucoma (POAG) progression. We analyzed microRNAs (miRNAs) expression profiling in aqueous humor (AH) of both POAG patients and normal controls, using a microarray-based approach. Subsequently, differentially expressed miRNAs (DEmiRNAs) were identified using Bayes moderated t-test. Next, DEmiRNAs target genes were predicted based on miRNA databases, followed by GO analysis and pathway analysis using DAVID. Furthermore, OAG-related genes analysis for target genes was carried out using CTD database, respectively. Finally, verification of DEmiRNAs expression levels was performed by RT-qPCR. A total of 40 significant DEmiRNAs were identified between control and POAG groups, including 24 up-regulated miRNAs and 16 down-regulated miRNAs. Further, the target genes of hsa-miR-206, including BMP2, SMAD4, ID2, and TNF, were mainly enriched in transforming growth factor-β (TGF-β) signaling pathway. While, target genes of hsa-miR-184, hsa-miR-34c-5p, hsa-miR-7-2-3p and hsa-miR-20b-3p, including BCL2, EPHB2, VEGFA, COL4A1, APC, and TGFBR1, were enriched in eye development. Moreover, FNDC3B, CAV2 and VEGF, target genes of hsa-miR-206 or hsa-miR-34c-5p, were the OAG-related genes. Ultimately, RT-qPCR analysis confirmed that mRNA levels of hsa-miR-206, hsa-miR-7-2-3p, and hsa-miR-20b-3p were increased, while those of hsa-miR-184 and hsa-miR-34c-5p were decreased in POAG compared with normal groups (P < 0.05). Hsa-miR-206, hsa-miR-184, hsa-miR-34c-5p, hsa-miR-7-2-3p and hsa-miR-20b-3p might play a significant role in the pathogenesis of POAG and hsa-miR-206 might be associated with the development of POAG by regulating TGF-β signaling pathway. These results might provide insight toward a better understanding of the pathogenesis of POAG.
2015-08-04 | GSE71639 | GEO
Project description:Cardiovascular disease (CVD) accounts for the majority of deaths in patients with type 1 diabetes (T1D); however, the determinants of plaque composition are unknown in this population. MicroRNAs (miRNAs), the most abundant class of circulating small non-coding RNA (sncRNAs) regulating gene expression, participate in the development of atherosclerosis and represent promising biomarkers of CVD. This study analyzed the circulating miRNA expression profile in T1D with carotid calcified and fibrous plaque. We identified four upregulated (miR-503-5p, let-7d-5p, miR-106b-3p, miR-93-5p) and one downregulated (miR-10a-5p) miRNAs in patients with calcified plaque(s) compared to those with fibrous plaque(s). ROC curve analysis demonstrated that miR-503-5p and miR-10a-5p discriminate with good performance in the different plaque compositions. miR-503-3p inversely and miR-10a-5p directly correlate with LDL cholesterol concentrations. Pathway enrichment analysis of putative gene targets of selected miRNAs revealed involvement in apoptotic and inflammatory processes regulation, osteogenic differentiation, and vascular calcification. These findings comprehensively characterize miRNAs and their signature in the regulatory network, leading to different plaque compositions in T1D. These results could have important clinical implications for developing novel therapeutic strategies to prevent CVD in diabetes.
2022-07-14 | GSE207901 | GEO
Project description:Hyperglycemia is a hallmark in prediabetes and type 2 diabetes mellitus (T2DM) which increases risk of micro and macrovascular complications such as diabetic retinopathy, diabetic nephropathy (microvascular complications), and peripheral vascular disease, cerebrovascular disease and cardiovascular diseases (macrovascular complications). Endothelial cells are affected in both cases. In this study, we investigated the miRNA expression changes in HUVECs during different glucose treatment (5mM, 10mM, 25mM and 40mM glucose) at various time intervals (6, 12, 24 and 48hrs). The results of miRNA microarray showed there is a correlation between hyperglycemia induced endothelial dysfunction and miRNA expression. In silico prediction showed that the following pathways: Regulation of actin cytoskeleton, PI3K-Akt signaling pathway, Apoptosis, Neurotrophin signaling pathway, and Insulin signaling pathway, were dysregulated during hyperglycemia. Majority of the pathways are related to apoptosis. 10 miRNAs (miR-26a-5p, -26b-5p, 29b-3p, 29c-3p, 125b-1-3p, -130b-3p, - 140-5p, -221-3p, -192-5p, and -320a,) showed increased expression with increasing concentration of glucose treatment. miR-26a-5p, -29b-3p, - 140-5p, -221-3p, and -192-5p are involves in endothelial apoptosis. Our study revealed miRNAs (miR-29b-3p and – 192-5p) with known mRNA targets (BCL2 and MCL1) showed expression pattern inversely correlating with their respective target mRNAs. Therefore these miRNAs could involve in the endothelial dysfunction due to hyperglycemia.
2016-05-23 | GSE74296 | GEO
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2021-06-14 | GSE174224 | GEO
Project description:We investigate the expression of miRNA in exosome of EBV-positive gastric carcinoma cells. The exosomes of EBV-positive and negative gastric carcinoma cells were separated by ultracentrifugation, the morphology of exosomes was identified by transmission electron microscopy, the exosome size was analyzed by Nanosight, and the expression of exosome membrane protein CD63 and CD81 was detected by western blot. High-throughput sequencing was used to detect miRNA expression profiles in gastric cancer cell lines and their exosomes. Under the ultra-microscopic electron microscope, the exosomes are seen as a typical translucent cup-like structure or a flat spherical structure. The nanoparticle tracking analyzer (Nanosight) showed that the exosomes were between 30 and 150 nm in diameter. Western blot(WB) assays showed that exosomes secreted by EBVaGC and EBVnGC cells expressed specific exosome membrane-associated proteins CD63 and CD81. High-throughput sequencing revealed that EBVaGC(SNU-719) and EBVnGC(AGS) and their secreted exosomes were highly expressed with certain human miRNAs, among which AGS-exo was highly expressed with hsa-miR-23b-3p, hsa-miR-320a-3p, and hsa-miR-4521. SNU-719-exo was highly expressed as hsa-miR-21-5p, hsa-miR-148a-3p and hsa-miR-7-5p. Nearly all EBV-related miRNAs (EBV-miRNA) were expressed in SNU-719 cells and their exosomes, among which EBV-miR-BART1-5p, EBV-miR-BART17-3p and EBV-miR-BART18-5p were the highest in SNU-719 cells, EBV-miR-BART1-5p, EBV-miR-BART18-5p and EBV-miR-BART17-3p were the highest in SNU-719-exo.
2022-03-14 | GSE198354 | GEO