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Potential Relationship between Clinical Significance and Serum Exosomal miRNAs in Patients with Multiple Myeloma.

ABSTRACT: This study evaluated the potential relationship between exosomal miRNAs and clinical symptoms in patients with multiple myeloma (MM). Forty-eight newly diagnosed myeloma patients and sixteen normal donors were enrolled in the study. The results showed that the relative expression levels of let-7c-5p, let-7d-5p, miR-140-3p, miR-185-5p, and miR-425-5p in the exosomes of MM patients were significantly lower than those of healthy controls. Furthermore, there were significant differences in the clinical characteristics of myeloma, such as kidney damage, while the expression levels of the same miRNA in exosomes and serum are not correlated. The expression of exosomal miRNA is related to the expression levels of clinical feature-related factors, such as creatinine, ?2-microglobulin, ?-CTX, and IL-6 in serum. Establishing this relationship could contribute to understanding the pathogenesis of MM.

SUBMITTER: Zhang ZY

PROVIDER: S-EPMC6931021 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Potential Relationship between Clinical Significance and Serum Exosomal miRNAs in Patients with Multiple Myeloma.

Zhang Zhi-Yao ZY Li Yan-Chen YC Geng Chuan-Ying CY Wang Hui-Juan HJ Chen Wen-Ming WM

BioMed research international 20191214

This study evaluated the potential relationship between exosomal miRNAs and clinical symptoms in patients with multiple myeloma (MM). Forty-eight newly diagnosed myeloma patients and sixteen normal donors were enrolled in the study. The results showed that the relative expression levels of let-7c-5p, let-7d-5p, miR-140-3p, miR-185-5p, and miR-425-5p in the exosomes of MM patients were significantly lower than those of healthy controls. Furthermore, there were significant differences in the clini ...[more]

PMID: 31915680

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Project description:Colorectal cancer (CRC) is the most common malignant gastrointestinal tumor worldwide. Serum exosomal microRNAs (miRNAs) play a critical role in tumor progression and metastasis. However, the underlying molecular mechanisms are poorly understood.The miRNAs expression profile (GSE39833) was downloaded from Gene Expression Omnibus (GEO) database. GEO2R was applied to screen the differentially expressed miRNAs (DEmiRNAs) between healthy and CRC serum exosome samples. The target genes of DEmiRNAs were predicted by starBase v3.0 online tool. The gene ontology (GO) and Kyoto Encyclopedia of Genomes pathway (KEGG) enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. The protein-protein interaction (PPI) network was established by the Search Tool for the Retrieval of Interacting Genes (STRING) visualized using Cytoscape software. Molecular Complex Detection (MCODE) and cytohubba plug-in were used to screen hub genes and gene modules.In total, 102 DEmiRNAs were identified including 67 upregulated and 35 downregulated DEmiRNAs, and 1437 target genes were predicted. GO analysis showed target genes of upregulated DEmiRNAs were significantly enriched in transcription regulation, protein binding, and ubiquitin protein ligase activity. While the target genes of downregulated DEmiRNAs were mainly involved in transcription from RNA polymerase II promoter, SMAD binding, and DNA binding. The KEGG pathway enrichment analyses showed target genes of upregulated DEmiRNAs were significantly enriched in proteoglycans in cancer, microRNAs in cancer, and phosphatidylinositol-3 kinases/Akt (PI3K-Akt) signaling pathway, while target genes of downregulated DEmiRNAs were mainly enriched in transforming growth factor-beta (TGF-beta) signaling pathway and proteoglycans in cancer. The genes of the top 3 modules were mainly enriched in ubiquitin mediated proteolysis, spliceosome, and mRNA surveillance pathway. According to the cytohubba plugin, 37 hub genes were selected, and 4 hub genes including phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), SRC, cell division cycle 42 (CDC42), E1A binding protein p300 (EP300) were identified by combining 8 ranked methods of cytohubba.The study provides a comprehensive analysis of exosomal DEmiRNAs and target genes regulatory network in CRC, which can better understand the roles of exosomal miRNAs in the development of CRC. However, these findings require further experimental validation in future studies.

Project description:IntroductionMyocardial damage is a mostly incurable complication of multiple myeloma (MM) that seriously affects the treatment outcome and quality of life of patients. Exosomal circular RNAs (exo-circRNAs) play an important role in tumor occurrence and development and are considered key factors in MM pathogenesis. However, the role and mechanism of action of exo-circRNAs in MM-related myocardial damage are still unclear. This study aimed to investigate correlations between exo-circRNAs and MM and to preliminarily explore the role of exo-circRNAs in MM-related myocardial damage.MethodsSix MM patients and five healthy controls (HCs) were included in the study. High-throughput sequencing and qRT-PCR verification were used to obtain a profile of abnormally expressed exo-circRNAs. GO, KEGG, miRanda, TargetScan and Metascape were used for bioinformatics analyses. H9C2 cells treated with exosomes from U266 cells were used in cell experiments. CCK-8, PCR, immunofluorescence and western blotting assays were used to detect cell proliferation and expression of autophagy-related indicators. Electron microscopy was used to observe the number of autophagic vesicles.ResultsBioinformatics analysis showed that circRNAs with upregulated expression had the potential to promote MM-related myocardial damage. In addition, PCR results confirmed that circ-G042080 was abundantly expressed in the serum exosomes of 20 MM patients. Correlation analysis showed that the expression level of circ-G042080 was positively correlated with the clinical level of MM and MM-related myocardial damage and that circ-G042080 might interfere with MM-related myocardial damage through a downstream miRNA/TLR4 axis. Cell experiments demonstrated that the circ-G042080/hsa-miR-4268/TLR4 axis might exist in H9C2 cells incubated with exosomes and cause abnormal autophagy.ConclusionAbnormal expression of serum exo-circRNAs was found to be associated with MM-related myocardial damage, suggesting that exo-circRNAs might become a new diagnostic marker of MM-related myocardial damage and a therapeutic target.

Dataset Information

Potential Relationship between Clinical Significance and Serum Exosomal miRNAs in Patients with Multiple Myeloma.

Publications

Potential Relationship between Clinical Significance and Serum Exosomal miRNAs in Patients with Multiple Myeloma.

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