scholarly journals Circulating miRNA Profiling in Plasma Samples of Ovarian Cancer Patients

2019 ◽  
Vol 20 (18) ◽  
pp. 4533 ◽  
Author(s):  
András Penyige ◽  
Éva Márton ◽  
Beáta Soltész ◽  
Melinda Szilágyi-Bónizs ◽  
Róbert Póka ◽  
...  

Ovarian cancer is one of the most common cancer types in women characterized by a high mortality rate due to lack of early diagnosis. Circulating miRNAs besides being important regulators of cancer development could be potential biomarkers to aid diagnosis. We performed the circulating miRNA expression analysis in plasma samples obtained from ovarian cancer patients stratified into FIGO I, FIGO III, and FIGO IV stages and from healthy females using the NanoString quantitative assay. Forty-five miRNAs were differentially expressed, out of these 17 miRNAs showed significantly different expression between controls and patients, 28 were expressed only in patients, among them 19 were expressed only in FIGO I patients. Differentially expressed miRNAs were ranked by the network-based analysis to assess their importance. Target genes of the differentially expressed miRNAs were identified then functional annotation of the target genes by the GO and KEGG-based enrichment analysis was carried out. A general and an ovary-specific protein–protein interaction network was constructed from target genes. Results of our network and the functional enrichment analysis suggest that besides HSP90AA1, MYC, SP1, BRCA1, RB1, CFTR, STAT3, E2F1, ERBB2, EZH2, and MET genes, additional genes which are enriched in cell cycle regulation, FOXO, TP53, PI-3AKT, AMPK, TGFβ, ERBB signaling pathways and in the regulation of gene expression, proliferation, cellular response to hypoxia, and negative regulation of the apoptotic process, the GO terms have central importance in ovarian cancer development. The aberrantly expressed miRNAs might be considered as potential biomarkers for the diagnosis of ovarian cancer after validation of these results in a larger cohort of ovarian cancer patients.

2021 ◽  
Author(s):  
Li Xia ◽  
Huang He

Abstract Backguound: To screen the signaling axis of epigenetic modification in serum exosomes of ovarian cancer patients based on sequencing technology and raw signal analysis, in depth study of the potential mechanism of action of ovarian cancer, prediction of potential therapeutic targets and survival prognosis analysis of potential targets.Methods: Serum exosomes from three ovarian cancer patients were selected as the experimental group, and serum exosomes from three uterine fibroid patients as the control group, and whole transcriptome of serum exosomes was performed to obtain differentially expressed lncRNA and mRNA in ovarian cancer,The miRcode database and miRNA target gene prediction website were used to predict the target genes, Cytoscape software was used to draw a ceRNA network model of epigenetic modification of ovarian cancer serum exosomes, and the R language was used for GO and KEGG enrichment analysis of the target genes. Finally, the TCGA website was used to download clinical and expression data related to ovarian cancer, and the common potential target genes obtained in the previous period were analyzed for survival。Results: A total of 117 differentially expressed lncRNAs as well as 513 differentially expressed mRNAs (P < 0.05, |log2 FC|≥ 1.0) were obtained by combining sequencing data and raw signal analysis, and 841 predicted target genes were reciprocally mapped by combining mircode database and miRNA target gene prediction website, resulting in 11 potential target genes related to ovarian cancer (FGFR3, BMPR1B, TRIM29, FBN2, PAPPA, CCDC58, IGSF3, FBXO10, GPAM, HOXA10, LHFPL4), and survival prognosis analysis of the above 11 target genes revealed that the survival curve was statistically significant (P < 0.05) for HOXA10 only genes, but not for the other genes, and through enrichment analysis, we found that the above target genes were mainly involved in biological processes such as regulation of transmembrane receptor protein kinase activity, structural molecule activity with elasticity, transforming growth factor - activated receptor activity, and GABA receptor binding, and were mainly enriched in signaling pathways regulating stem cell pluripotency, bladder cancer, glycerolipid metabolism, central carbon metabolism of cancer, tyrosine stimulation to EGFR in signaling pathways such as resistance to enzyme inhibitors.Conclusions: The serum exosomal DIO3OS-hsa-miR-27a-3p-HOXA10 epigenetic modification signaling axis affects ovarian cancer development and disease survival prognosis by targeting transcriptional dysregulation pathways in cancer.


2021 ◽  
Vol 15 (8) ◽  
pp. 927-936 ◽  
Author(s):  
Yan Peng ◽  
Yuewu Liu ◽  
Xinbo Chen

Background: Drought is one of the most damaging and widespread abiotic stresses that can severely limit the rice production. MicroRNAs (miRNAs) act as a promising tool for improving the drought tolerance of rice and have become a hot spot in recent years. Objective: In order to further extend the understanding of miRNAs, the functions of miRNAs in rice under drought stress are analyzed by bioinformatics. Method: In this study, we integrated miRNAs and genes transcriptome data of rice under the drought stress. Some bioinformatics methods were used to reveal the functions of miRNAs in rice under drought stress. These methods included target genes identification, differentially expressed miRNAs screening, enrichment analysis of DEGs, network constructions for miRNA-target and target-target proteins interaction. Results: (1) A total of 229 miRNAs with differential expression in rice under the drought stress, corresponding to 73 rice miRNAs families, were identified. (2) 1035 differentially expressed genes (DEGs) were identified, which included 357 up-regulated genes, 542 down-regulated genes and 136 up/down-regulated genes. (3) The network of regulatory relationships between 73 rice miRNAs families and 1035 DEGs was constructed. (4) 25 UP_KEYWORDS terms of DEGs, 125 GO terms and 7 pathways were obtained. (5) The protein-protein interaction network of 1035 DEGs was constructed. Conclusion: (1) MiRNA-regulated targets in rice might mainly involve in a series of basic biological processes and pathways under drought conditions. (2) MiRNAs in rice might play critical roles in Lignin degradation and ABA biosynthesis. (3) MiRNAs in rice might play an important role in drought signal perceiving and transduction.


2019 ◽  
Vol 47 (8) ◽  
pp. 3580-3589 ◽  
Author(s):  
Yingyuan Li ◽  
Wulin Tan ◽  
Fang Ye ◽  
Faling Xue ◽  
Shaowei Gao ◽  
...  

Objective We aimed to explore potential microRNAs (miRNAs) and target genes related to atrial fibrillation (AF). Methods Data for microarrays GSE70887 and GSE68475, both of which include AF and control groups, were downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs between AF and control groups were identified within each microarray, and the intersection of these two sets was obtained. These miRNAs were mapped to target genes in the miRNet database. Functional annotation and enrichment analysis of these target genes was performed in the DAVID database. The protein-protein interaction (PPI) network from the STRING database and the miRNA-target-gene network were merged into a PPI-miRNA network using Cytoscape software. Modules of this network containing miRNAs were detected and further analyzed. Results Ten differentially expressed miRNAs and 1520 target genes were identified. Three PPI-miRNA modules were constructed, which contained miR-424, miR-15a, miR-542-3p, and miR-421 as well as their target genes, CDK1, CDK6, and CCND3. Conclusion The identified miRNAs and genes may be related to the pathogenesis of AF. Thus, they may be potential biomarkers for diagnosis and targets for treatment of AF.


Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 417
Author(s):  
Chuanxi Peng ◽  
Xing Wang ◽  
Tianyu Feng ◽  
Rui He ◽  
Mingcai Zhang ◽  
...  

MicroRNAs (miRNAs), the post-transcriptional gene regulators, are known to play an important role in plant development. The identification of differentially expressed miRNAs could better help us understand the post-transcriptional regulation that occurs during maize internode elongation. Accordingly, we compared the expression of MIRNAs between fixed internode and elongation internode samples and classified six differentially expressed MIRNAs as internode elongation-responsive miRNAs including zma-MIR160c, zma-MIR164b, zma-MIR164c, zma-MIR168a, zma-MIR396f, and zma-MIR398b, which target mRNAs supported by transcriptome sequencing. Functional enrichment analysis for predictive target genes showed that these miRNAs were involved in the development of internode elongation by regulating the genes respond to hormone signaling. To further reveal how miRNA affects internode elongation by affecting target genes, the miRNA–mRNA–PPI (protein and protein interaction) network was constructed to summarize the interaction of miRNAs and these target genes. Our results indicate that miRNAs regulate internode elongation in maize by targeting genes related to cell expansion, cell wall synthesis, transcription, and regulatory factors.


2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Hao Zhang ◽  
Xi Chen ◽  
Yufeng Yuan

Purpose. To identify pivotal differentially expressed miRNAs and genes and construct their regulatory network in hepatocellular carcinoma. Methods. mRNA (GSE101728) and microRNA (GSE108724) microarray datasets were obtained from the NCBI Gene Expression Omnibus (GEO) database. Then, we identified the differentially expressed miRNAs and mRNAs. Sequentially, transcription factor enrichment and gene ontology (GO) enrichment analysis for miRNA were performed. Target genes of these differential miRNAs were obtained using packages in R language ( R package multiMiR). After that, downregulated miRNAs were matched with target mRNAs which were upregulated, while upregulated miRNAs were paired with downregulated target mRNA using scripts written in Perl. An miRNA-mRNA network was constructed and visualized in Cytoscape software. For miRNAs in the network, survival analysis was performed. And for genes in the network, we did gene ontology (GO) and KEGG pathway enrichment analysis. Results. A total of 35 miRNAs and 295 mRNAs were involved in the network. These differential genes were enriched in positive regulation of cell-cell adhesion, positive regulation of leukocyte cell-cell adhesion, and so on. Eight differentially expressed miRNAs were found to be associated with the OS of patients with HCC. Among which, miR-425 and miR-324 were upregulated while the other six, including miR-99a, miR-100, miR-125b, miR-145, miR-150, and miR-338, were downregulated. Conclusion. In conclusion, these results can provide a potential research direction for further studies about the mechanisms of how miRNA affects malignant behavior in hepatocellular carcinoma.


2018 ◽  
Vol 50 (2) ◽  
pp. 552-568 ◽  
Author(s):  
Xuehui Yang ◽  
Hongmei Chen ◽  
Yan Chen ◽  
Yochai Birnbaum ◽  
Rongbi Liang ◽  
...  

Background/Aims: Circulating miRNAs could serve as biomarkers for diagnosis or prognosis of heart diseases and cerebrovascular diseases. Dexmedetomidine has protective effects in various organs. The effects of dexmedetomidine on circulating miRNAs remain unknown. Here, we investigated differentially expressed miRNA and to predict the target genes of the miRNA in patients receiving dexmedetomidine. Methods: The expression levels of circulating miRNAs of 3 patients were determined through high through-put miRNA sequencing technology. Target genes of the identified differentially expressed miRNAs were predicted using TargetScan 7.1 and miRDB v.5. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to conduct functional annotation and pathway enrichment analysis of target genes respectively. Results: Twelve differentially expressed miRNAs were identified. Five miRNAs were upregulated (hsa-miR-4508, hsa-miR-novel-chr8_87373, hsa-miR-30a-3p, hsa-miR-novel-chr16_26099, hsa-miR-4306) and seven miRNAs (hsa-miR-744-5p, hsa-miR-320a, hsa-miR-novel-chr9_90035, hsa-miR-101-3p, hsa-miR-150-5p, hsa-miR-342-3p, and hsa-miR-140-3p) were downregulated after administration of dexmedetomidine in the subjects. The target genes and pathways related to the differentially expressed miRNAs were predicted and analyzed. Conclusion: The differentially expressed miRNAs may be involved in the mechanisms of action of dexmedetomidine. Specific miRNAs, such as hsa-miR-101-3p, hsa-miR-150-5p and hsa-miR-140-3p, are new potential targets for further functional studies of dexmedetomidine.


2021 ◽  
Vol 22 (10) ◽  
pp. 5058
Author(s):  
Dóra Géczi ◽  
Bálint Nagy ◽  
Melinda Szilágyi ◽  
András Penyige ◽  
Álmos Klekner ◽  
...  

(1) Background: Glioblastoma multiforme (GBM) is among the most aggressive cancers with a poor prognosis. Treatment options are limited, clinicians lack efficient prognostic and predictive markers. Circulating miRNAs—besides being important regulators of cancer development—may have potential as diagnostic biomarkers of GBM. (2) Methods: In this study, profiling of 798 human miRNAs was performed on blood plasma samples from 6 healthy individuals and 6 patients with GBM, using a NanoString nCounter Analysis System. To validate our results, five miRNAs (hsa-miR-433-3p, hsa-miR-362-3p, hsa-miR-195-5p, hsa-miR-133a-3p, and hsa-miR-29a-3p) were randomly chosen for RT-qPCR detection. (3) Results: In all, 53 miRNAs were significantly differentially expressed in plasma samples of GBM patients when data were filtered for FC 1 and FDR 0.1. Target genes of the top 39 differentially expressed miRNAs were identified, and we carried out functional annotation and pathway enrichment analysis of target genes via GO and KEGG-based tools. General and cortex-specific protein–protein interaction networks were constructed from the target genes of top miRNAs to assess their functional connections. (4) Conclusions: We demonstrated that plasma microRNA profiles are promising diagnostic and prognostic molecular biomarkers that may find an actual application in the clinical practice of GBM, although more studies are needed to validate our results.


Author(s):  
Maria Vulf ◽  
Daria Shunkina ◽  
Aleksandra Komar ◽  
Maria Bograya ◽  
Pavel Zatolokin ◽  
...  

Non-alcoholic fatty liver disease (NAFLD) is emerging as one of the most common chronic liver diseases worldwide, affecting 25% of the world population. In recent years, there has been increasing evidence for the involvement of microRNAs in the epigenetic regulation of genes taking part in the development of steatosis and steatohepatitis—two main stages of NAFLD pathogenesis. In the present study, miRNA profiles were studied in groups of patients with steatosis and steatohepatitis to compare the characteristics of RNA-dependent epigenetic regulation of the stages of NAFLD development. According to the results of miRNA screening, 23 miRNAs were differentially expressed serum in a group of patients with steatohepatitis and 2 in a group of patients with steatosis. MiR-195-5p and miR-16-5p are common differentially expressed miRNAs for both steatosis and steatohepatitis. We analyzed the obtained results: the search for target genes for the differentially expressed miRNAs in our study and the subsequent gene set enrichment analysis performed on KEGG and REACTOME databases revealed which metabolic pathways undergo changes in RNA-dependent epigenetic regulation in steatosis and steatohepatitis. New findings within the framework of this study are the dysregulation of neurohumoral pathways in the pathogenesis of NAFLD as an object of changes in RNA-dependent epigenetic regulation. The miRNAs differentially expressed in our study were found to target 7% of genes in the classic pathogenesis of NAFLD in the group of patients with steatosis and 50% in the group of patients with steatohepatitis. The effects of these microRNAs on genes for the pathogenesis of NAFLD were analyzed in detail. MiR-374a-5p, miR-1-3p and miR-23a-3p do not target genes directly involved in the pathogenesis of NAFLD. The differentially expressed miRNAs found in this study target genes largely responsible for mitochondrial function. The role of miR-423-5p, miR-143-5p and miR-200c-3 in regulating apoptotic processes in the liver and hepatocarcinogenesis is of interest for future experimental studies. These miR-374a, miR-143, miR-1, miR-23a, and miR-423 have potential for steatohepatitis diagnosis and are poorly studied in the context of NAFLD. Thus, this work opens up prospects for further studies of microRNAs as diagnostic and therapeutic biomarkers for NAFLD.


2021 ◽  
Author(s):  
Chengxin Zhu ◽  
Jingze Xu ◽  
Shu Cao ◽  
Changqing Yang ◽  
Renhu Li ◽  
...  

Abstract Background: More and more studies have shown that exosomes are involved in many aspects of bone metabolism. As the content of exosomes, miRNA plays an important role in the early diagnosis, treatment and prognosis evaluation of osteoporosis.Objective: To determine the potential molecular markers of osteoporosis by analyzing the differences of plasma exosome miRNA expression between postmenopausal women with osteoporosis and healthy controls.Methods: Serum samples of postmenopausal osteoporosis (PMOP) patients over 65 years old (n = 12) and healthy controls (n = 12) were collected. The exosomes were separated by molecular size exclusion chromatography(SEC).The differentially expressed miRNAs were analyzed by cluster analysis. The target genes of miRNAs were predicted and annotated by relevant software.The target genes were classified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The appropriate biomarkers were screened out.Results: The miRNA spectrum of the patients was significantly different from that of the control group. Validation studies showed that 14 up-regulated miRNAs had a high probability of prediction, which could distinguish osteoporosis patients from healthy controls. Thirty-one genes were predicted to be targets for these miRNAs. GO enrichment analysis showed that miRNAs were mainly concentrated in protein binding, carbohydrate-binding, chromatin binding and protein kinase binding. KEGG enrichment analysis showed that miRNAs were mainly concentrated in the p53 signalling pathway, mineral absorption, glycerin metabolism, insulin secretion, glycosaminoglycan biosynthesis heparin sulfate /heparin pathway. This study identified a large number of differentially expressed miRNAs in plasma samples from postmenopausal women with osteoporosis. It may help to obtain new diagnosis and treatment strategies for PMOP.Conclusion: Our study identified the characteristics of plasma miRNAs in patients with osteoporosis and identified 14 candidate miRNAs, which may be useful biomarkers of osteoporosis. We speculate that these differentially expressed miRNAs may play a key role in the process of bone marrow mesenchymal stem cells osteogenic metabolism and transformation.


2021 ◽  
Author(s):  
Sangyeob Lee ◽  
Jun-Il Yoo

Abstract Background: Sarcopenia is an age-related disease with skeletal muscle loss, weakness, and functional impairment. The potential causes of sarcopenia including the programmed cell death of muscles, inflammation, reactive oxygen species, protein turnover, and mitochondrial dysfunction have been studied. The purpose of this study was to find differentially expressed miRNAs (DE-miRNAs) in the muscle samples of older people (GSE23527). In addition, we performed to identify new miRNA-mRNA regulatory network for treating sarcopeniaMethods: Gene expression profiles were obtained from microarray datasets (GSE8479 and GSE1428) of the vastus lateralis muscles of young and older male subjects. Dataset GSE23527 was derived from the platform of GPL10358 (LC_MRA-1001_miRHuman_11.0_080411) and contained microRNA arrays of 12 young muscle samples and 12 older muscle samples. The DEGs between the older and young GSE8479 and GSE1428 samples were identified using the online analysis tool imaGEO (https://imageo.genyo.es). Pathway and process enrichment analysis with the ontology sources in the KEGG pathway, GO biological processes, Reactome gene sets, WikiPathways, and CORUM were analyzed by Metascape. A PPI (protein-protein interaction) network of DEGs was constructed using the Search Tool for Retrieval of Interacting Genes (STRING) app in Cytoscape software (version 1.6.0). GEO2R (https://www.ncbi.nlm.nih.gov) was used to select differentially expressed miRNAs (DE-miRNAs) in the GSE 23527 dataset.Results: In the GSE8479 and GSE1428 datasets, a total of 81 DEGs were discovered, including four upregulated genes and 77 downregulated genes. The top 12 clusters and their representative enriched terms were identified using Metascape. A total of 79 nodes and 186 edges were predicted in the PPI network. One upregulated DE-miRNA (hsa-miR-450a-5p) and six downregulated DE-miRNAs (hsa-miR-127-3p, hsa-miR-24-2-5p, hsa-miR-378a-5p, hsa-miR-532-5p, hsa-miR-487b-5p, and has-miR-487b-3p) were selected in the miRBase database. The MiRWalk online database was utilized for exploring 8017 genes that were selected as genes regulated by DE-miRNAs and six of them overlapped with hub genes. COX7A1 and NDUFB5 showed significantly low expression in sarcopenia patients compared to the controls. COX7B and PDHA1 also displayed low expression in sarcopenia patients, but expression of COX7A1 and NDUFB5 was not significant. TIMM8A and CS showed similar expression rates in both samples.Conclusions: The present bioinformatics analysis showed that two target genes (COX7A1 and NDUFB5) were potentially downregulated in sarcopenia patients. These two genes could be the cause of sarcopenia with aging. In addition, present study showed that several miRNAs (hsa-miR-378a-5p, hsa-miR-532-5p, hsa-miR-127-3p, and hsa-miR-24-2-5p) were identified as regulating the target genes. These results suggest that controlling the identified miRNAs could be a prospective strategy for treating sarcopenia by regulating the mRNA-miRNA network.


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