Integrated analysis of circRNA-miRNA-mRNA regulatory network identifies potential diagnostic biomarkers in diabetic foot ulcer

Diabetic foot ulcer (DFU) is a common and serious complication of diabetes mellitus, which influences patients’ quality of life. Recently, circRNA regulated the mRNA levels by functioning as miRNA sponge in various disease, including diabetes mellitus. Nevertheless, the circRNA-miRNA-mRNA regulatory...

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Main Authors: Shuping Liao, Xiaolan Lin, Changyu Mo
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2020-09-01
Series:Non-coding RNA Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2468054020300524
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author Shuping Liao
Xiaolan Lin
Changyu Mo
author_facet Shuping Liao
Xiaolan Lin
Changyu Mo
author_sort Shuping Liao
collection DOAJ
description Diabetic foot ulcer (DFU) is a common and serious complication of diabetes mellitus, which influences patients’ quality of life. Recently, circRNA regulated the mRNA levels by functioning as miRNA sponge in various disease, including diabetes mellitus. Nevertheless, the circRNA-miRNA-mRNA regulatory network involved in DFU remains obscure. The aim of this study is to construct a competing endogenous RNA (ceRNA) network and screen biological indicators as diagnostic factors in DFU.All the differentially expressed circRNAs, miRNAs and mRNAs were derived from Gene Expression Omnibus database. Furthermore, circRNAs identified by cytoHubba analysis and miRNAs obtained by human miRNA-disease database were used to construct DFU-specific ceRNA network with intersection of mRNAs. Functional enrichment analysis displayed the function and pathway of dysregulated mRNAs. Hub genes with high diagnostic value were screened by ClusterONE, GO semantic similarity and receiver operating characteristic (ROC) curve.Here, the ceRNA network consisted of 8 circRNAs, 11 miRNAs and 91 mRNAs. Functional enrichment analysis demonstrated diabetic complications-related pathway including TGF-beta, FoxO and Wnt signaling pathway. GO semantic similarity and ROC curve analysis showed 6 hub genes with high diagnostic value (the area under the ROC curve ≥ 0.8) in patients with DFU, including BCL2, CCND1, IRAK4, SMAD4, SP1 and SUFU, which were identified as potential target genes for DFU diagnosis. In conclusion, the present study looked at a circRNA-miRNA-mRNA regulatory network with DFU and screened the potential function of mRNA, then identified novel diagnostic biomarkers and therapeutic targets for patients with DFU.
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spelling doaj.art-27e58816ec2641db917ae427442d30fc2024-04-16T19:01:55ZengKeAi Communications Co., Ltd.Non-coding RNA Research2468-05402020-09-0153116124Integrated analysis of circRNA-miRNA-mRNA regulatory network identifies potential diagnostic biomarkers in diabetic foot ulcerShuping Liao0Xiaolan Lin1Changyu Mo2Department of Health Management, Shenzhen People's Hospital, Shenzhen, Guangdong, 518020, ChinaDepartment of Health Management, Shenzhen People's Hospital, Shenzhen, Guangdong, 518020, ChinaDepartment of Health Management, Shenzhen People's Hospital, Shenzhen, Guangdong, 518020, China; Department physical examination, Baoan People's Hospital, Shenzhen, Guangdong, 518101, China; Corresponding author. Department of Health Management, Shenzhen People's Hospital, Shenzhen, Guangdong, 518020, China.Diabetic foot ulcer (DFU) is a common and serious complication of diabetes mellitus, which influences patients’ quality of life. Recently, circRNA regulated the mRNA levels by functioning as miRNA sponge in various disease, including diabetes mellitus. Nevertheless, the circRNA-miRNA-mRNA regulatory network involved in DFU remains obscure. The aim of this study is to construct a competing endogenous RNA (ceRNA) network and screen biological indicators as diagnostic factors in DFU.All the differentially expressed circRNAs, miRNAs and mRNAs were derived from Gene Expression Omnibus database. Furthermore, circRNAs identified by cytoHubba analysis and miRNAs obtained by human miRNA-disease database were used to construct DFU-specific ceRNA network with intersection of mRNAs. Functional enrichment analysis displayed the function and pathway of dysregulated mRNAs. Hub genes with high diagnostic value were screened by ClusterONE, GO semantic similarity and receiver operating characteristic (ROC) curve.Here, the ceRNA network consisted of 8 circRNAs, 11 miRNAs and 91 mRNAs. Functional enrichment analysis demonstrated diabetic complications-related pathway including TGF-beta, FoxO and Wnt signaling pathway. GO semantic similarity and ROC curve analysis showed 6 hub genes with high diagnostic value (the area under the ROC curve ≥ 0.8) in patients with DFU, including BCL2, CCND1, IRAK4, SMAD4, SP1 and SUFU, which were identified as potential target genes for DFU diagnosis. In conclusion, the present study looked at a circRNA-miRNA-mRNA regulatory network with DFU and screened the potential function of mRNA, then identified novel diagnostic biomarkers and therapeutic targets for patients with DFU.http://www.sciencedirect.com/science/article/pii/S2468054020300524Diabetic foot ulcerceRNA networkDiagnosisBiomarkers
spellingShingle Shuping Liao
Xiaolan Lin
Changyu Mo
Integrated analysis of circRNA-miRNA-mRNA regulatory network identifies potential diagnostic biomarkers in diabetic foot ulcer
Non-coding RNA Research
Diabetic foot ulcer
ceRNA network
Diagnosis
Biomarkers
title Integrated analysis of circRNA-miRNA-mRNA regulatory network identifies potential diagnostic biomarkers in diabetic foot ulcer
title_full Integrated analysis of circRNA-miRNA-mRNA regulatory network identifies potential diagnostic biomarkers in diabetic foot ulcer
title_fullStr Integrated analysis of circRNA-miRNA-mRNA regulatory network identifies potential diagnostic biomarkers in diabetic foot ulcer
title_full_unstemmed Integrated analysis of circRNA-miRNA-mRNA regulatory network identifies potential diagnostic biomarkers in diabetic foot ulcer
title_short Integrated analysis of circRNA-miRNA-mRNA regulatory network identifies potential diagnostic biomarkers in diabetic foot ulcer
title_sort integrated analysis of circrna mirna mrna regulatory network identifies potential diagnostic biomarkers in diabetic foot ulcer
topic Diabetic foot ulcer
ceRNA network
Diagnosis
Biomarkers
url http://www.sciencedirect.com/science/article/pii/S2468054020300524
work_keys_str_mv AT shupingliao integratedanalysisofcircrnamirnamrnaregulatorynetworkidentifiespotentialdiagnosticbiomarkersindiabeticfootulcer
AT xiaolanlin integratedanalysisofcircrnamirnamrnaregulatorynetworkidentifiespotentialdiagnosticbiomarkersindiabeticfootulcer
AT changyumo integratedanalysisofcircrnamirnamrnaregulatorynetworkidentifiespotentialdiagnosticbiomarkersindiabeticfootulcer