Construction of circRNA–miRNA–mRNA Network Reveal Functional circRNAs and Key Genes in Acute Myeloid Leukemia
Lianbo Hu,1 Bingrong Zheng,2 Yang Yang,2 Chunmei Chen,2 Meiwei Hu2 1Physical Examination Center, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Hematology, the Second Affiliated Hospital of Zhejiang...
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Dove Medical Press
2023-04-01
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author | Hu L Zheng B Yang Y Chen C Hu M |
author_facet | Hu L Zheng B Yang Y Chen C Hu M |
author_sort | Hu L |
collection | DOAJ |
description | Lianbo Hu,1 Bingrong Zheng,2 Yang Yang,2 Chunmei Chen,2 Meiwei Hu2 1Physical Examination Center, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Hematology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Meiwei Hu, Department of Hematology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, No. 318 Chaowang Road, Hangzhou, Zhejiang, 310014, People’s Republic of China, Email 20134013@zcmu.edu.cnIntroduction: CircRNA is closely correlated with a wide variety of processes of acute myeloid leukemia (AML), whereas the novel circRNAs, their molecular mechanism and the specific function they played in AML should be explored in depth.Methods: The microarray chip data of AML patients and normal samples in the Gene Expression Omnibus (GEO) database were selected to differentially expressed (DE) circRNA, miRNA, and mRNA genes. The miRNA gene was the intersection of the circRNA target gene predicted using CSCD and the miRNA gene screened from AML patients, while the mRNA gene was the intersection of the target gene mRNA of miRNA predicted using miRanda and miRTarBase software and the mRNA gene screened from AML patients. The hub mRNAs related to survival were further screened through Cox proportional hazard regression. CircRNA/miRNA/mRNA interaction network was constructed by using Cytoscape software.10 circRNAs and 6 miRNAs in bone marrow mononuclear cells (BMMNCs) of AML patients (n=43) and healthy controls (n=35) were determined by RT-qPCR. Correlations between them were analyzed by Pearson correlation coefficient.Results: 10 circRNAs, 6 miRNAs, and 33 mRNAs were identified. Subsequently, the network of circRNAs, miRNAs, and hub genes was built using Cystoscope. Four key circRNAs, seven hub genes and their regulatory pathways were identified. The result of RT-qPCRs showed that hsa_circ_0009581 and hsa_circ_0005273 were significantly upregulated in AML patients while hsa_circ_0000497 and hsa_circ_0001947 were significantly downregulated. Hsa-miR-150-5p was significantly downregulated; hsa-miR-454-3p was upregulated in AML patients. Hsa_circ_0009581 and hsa-miR-150-5p; hsa_ circ_0001947 and hsa-miR-454-3p were inversely correlated using Pearson’s correlation coefficient.Conclusion: This study suggests that differentially expressed circRNAs take on a critical significance to AML development and may be the effective therapeutic targets. We suppose that hsa_circ_0009581 promotes leukemia development through hsa-miR-150-5p and hsa_circ_0001947 through hsa-miR-454-3p. hsa_circ_0001947 and hsa_circ_0009581 may provide new directions in the pathogenesis of AML.Keywords: acute myeloid leukemia, circRNA, pathogenesis, bioinformation analysis |
first_indexed | 2024-04-09T15:53:55Z |
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last_indexed | 2024-04-09T15:53:55Z |
publishDate | 2023-04-01 |
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spelling | doaj.art-5006096ec364473a90c03c303015004b2023-04-25T18:55:18ZengDove Medical PressInternational Journal of General Medicine1178-70742023-04-01Volume 161491150483276Construction of circRNA–miRNA–mRNA Network Reveal Functional circRNAs and Key Genes in Acute Myeloid LeukemiaHu LZheng BYang YChen CHu MLianbo Hu,1 Bingrong Zheng,2 Yang Yang,2 Chunmei Chen,2 Meiwei Hu2 1Physical Examination Center, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Hematology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Meiwei Hu, Department of Hematology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, No. 318 Chaowang Road, Hangzhou, Zhejiang, 310014, People’s Republic of China, Email 20134013@zcmu.edu.cnIntroduction: CircRNA is closely correlated with a wide variety of processes of acute myeloid leukemia (AML), whereas the novel circRNAs, their molecular mechanism and the specific function they played in AML should be explored in depth.Methods: The microarray chip data of AML patients and normal samples in the Gene Expression Omnibus (GEO) database were selected to differentially expressed (DE) circRNA, miRNA, and mRNA genes. The miRNA gene was the intersection of the circRNA target gene predicted using CSCD and the miRNA gene screened from AML patients, while the mRNA gene was the intersection of the target gene mRNA of miRNA predicted using miRanda and miRTarBase software and the mRNA gene screened from AML patients. The hub mRNAs related to survival were further screened through Cox proportional hazard regression. CircRNA/miRNA/mRNA interaction network was constructed by using Cytoscape software.10 circRNAs and 6 miRNAs in bone marrow mononuclear cells (BMMNCs) of AML patients (n=43) and healthy controls (n=35) were determined by RT-qPCR. Correlations between them were analyzed by Pearson correlation coefficient.Results: 10 circRNAs, 6 miRNAs, and 33 mRNAs were identified. Subsequently, the network of circRNAs, miRNAs, and hub genes was built using Cystoscope. Four key circRNAs, seven hub genes and their regulatory pathways were identified. The result of RT-qPCRs showed that hsa_circ_0009581 and hsa_circ_0005273 were significantly upregulated in AML patients while hsa_circ_0000497 and hsa_circ_0001947 were significantly downregulated. Hsa-miR-150-5p was significantly downregulated; hsa-miR-454-3p was upregulated in AML patients. Hsa_circ_0009581 and hsa-miR-150-5p; hsa_ circ_0001947 and hsa-miR-454-3p were inversely correlated using Pearson’s correlation coefficient.Conclusion: This study suggests that differentially expressed circRNAs take on a critical significance to AML development and may be the effective therapeutic targets. We suppose that hsa_circ_0009581 promotes leukemia development through hsa-miR-150-5p and hsa_circ_0001947 through hsa-miR-454-3p. hsa_circ_0001947 and hsa_circ_0009581 may provide new directions in the pathogenesis of AML.Keywords: acute myeloid leukemia, circRNA, pathogenesis, bioinformation analysishttps://www.dovepress.com/construction-of-circrnamirnamrna-network-reveal-functional-circrnas-an-peer-reviewed-fulltext-article-IJGMacute myeloid leukemiacircrnapathogenesisbioinformation analysis |
spellingShingle | Hu L Zheng B Yang Y Chen C Hu M Construction of circRNA–miRNA–mRNA Network Reveal Functional circRNAs and Key Genes in Acute Myeloid Leukemia International Journal of General Medicine acute myeloid leukemia circrna pathogenesis bioinformation analysis |
title | Construction of circRNA–miRNA–mRNA Network Reveal Functional circRNAs and Key Genes in Acute Myeloid Leukemia |
title_full | Construction of circRNA–miRNA–mRNA Network Reveal Functional circRNAs and Key Genes in Acute Myeloid Leukemia |
title_fullStr | Construction of circRNA–miRNA–mRNA Network Reveal Functional circRNAs and Key Genes in Acute Myeloid Leukemia |
title_full_unstemmed | Construction of circRNA–miRNA–mRNA Network Reveal Functional circRNAs and Key Genes in Acute Myeloid Leukemia |
title_short | Construction of circRNA–miRNA–mRNA Network Reveal Functional circRNAs and Key Genes in Acute Myeloid Leukemia |
title_sort | construction of circrna ndash mirna ndash mrna network reveal functional circrnas and key genes in acute myeloid leukemia |
topic | acute myeloid leukemia circrna pathogenesis bioinformation analysis |
url | https://www.dovepress.com/construction-of-circrnamirnamrna-network-reveal-functional-circrnas-an-peer-reviewed-fulltext-article-IJGM |
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