Identification of transcription factors and construction of a novel miRNA regulatory network in primary osteoarthritis by integrated analysis

Abstract Backgrounds As osteoarthritis (OA) disease-modifying therapies are not available, novel therapeutic targets need to be discovered and prioritized. Here, we aim to identify miRNA signatures in patients to fully elucidate regulatory mechanism of OA pathogenesis and advance in basic understand...

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Autores principales:	Ying Jiang, Yi Shen, Liyan Ding, Shengli Xia, Liying Jiang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Osteoarthritis Circulating microRNAs RNA sequencing Bioinformatics analysis Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/3d9da812ff2a4031af6c48f78395e6be
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spelling	oai:doaj.org-article:3d9da812ff2a4031af6c48f78395e6be2021-12-05T12:18:26ZIdentification of transcription factors and construction of a novel miRNA regulatory network in primary osteoarthritis by integrated analysis10.1186/s12891-021-04894-21471-2474https://doaj.org/article/3d9da812ff2a4031af6c48f78395e6be2021-12-01T00:00:00Zhttps://doi.org/10.1186/s12891-021-04894-2https://doaj.org/toc/1471-2474Abstract Backgrounds As osteoarthritis (OA) disease-modifying therapies are not available, novel therapeutic targets need to be discovered and prioritized. Here, we aim to identify miRNA signatures in patients to fully elucidate regulatory mechanism of OA pathogenesis and advance in basic understanding of the genetic etiology of OA. Methods Six participants (3 OA and 3 controls) were recruited and serum samples were assayed through RNA sequencing (RNA-seq). And, RNA-seq dataset was analysed to identify genes, pathways and regulatory networks dysregulated in OA. The overlapped differentially expressed microRNAs (DEMs) were further screened in combination with the microarray dataset GSE143514. The expression levels of candidate miRNAs were further validated by quantitative real-time PCR (qRT-PCR) based on the GEO dataset (GSE114007). Results Serum samples were sequenced interrogating 382 miRNAs. After screening of independent samples and GEO database, the two comparison datasets shared 19 overlapped candidate micRNAs. Of these, 9 up-regulated DEMs and 10 down-regulated DEMs were detected, respectively. There were 236 target genes for up-regulated DEMs and 400 target genes for those down-regulated DEMs. For up-regulated DEMs, the top 10 hub genes were KRAS, NRAS, CDC42, GDNF, SOS1, PIK3R3, GSK3B, IRS2, GNG12, and PRKCA; for down-regulated DEMs, the top 10 hub genes were NR3C1, PPARGC1A, SUMO1, MEF2C, FOXO3, PPP1CB, MAP2K1, RARA, RHOC, CDC23, and CREB3L2. Mir-584-5p-KRAS, mir-183-5p-NRAS, mir-4435-PIK3R3, and mir-4435-SOS1 were identified as four potential regulatory pathways by integrated analysis. Conclusions We have integrated differential expression data to reveal putative genes and detected four potential miRNA-target gene pathways through bioinformatics analysis that represent new mediators of abnormal gene expression and promising therapeutic targets in OA.Ying JiangYi ShenLiyan DingShengli XiaLiying JiangBMCarticleOsteoarthritisCirculating microRNAsRNA sequencingBioinformatics analysisDiseases of the musculoskeletal systemRC925-935ENBMC Musculoskeletal Disorders, Vol 22, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Osteoarthritis Circulating microRNAs RNA sequencing Bioinformatics analysis Diseases of the musculoskeletal system RC925-935
spellingShingle	Osteoarthritis Circulating microRNAs RNA sequencing Bioinformatics analysis Diseases of the musculoskeletal system RC925-935 Ying Jiang Yi Shen Liyan Ding Shengli Xia Liying Jiang Identification of transcription factors and construction of a novel miRNA regulatory network in primary osteoarthritis by integrated analysis
description	Abstract Backgrounds As osteoarthritis (OA) disease-modifying therapies are not available, novel therapeutic targets need to be discovered and prioritized. Here, we aim to identify miRNA signatures in patients to fully elucidate regulatory mechanism of OA pathogenesis and advance in basic understanding of the genetic etiology of OA. Methods Six participants (3 OA and 3 controls) were recruited and serum samples were assayed through RNA sequencing (RNA-seq). And, RNA-seq dataset was analysed to identify genes, pathways and regulatory networks dysregulated in OA. The overlapped differentially expressed microRNAs (DEMs) were further screened in combination with the microarray dataset GSE143514. The expression levels of candidate miRNAs were further validated by quantitative real-time PCR (qRT-PCR) based on the GEO dataset (GSE114007). Results Serum samples were sequenced interrogating 382 miRNAs. After screening of independent samples and GEO database, the two comparison datasets shared 19 overlapped candidate micRNAs. Of these, 9 up-regulated DEMs and 10 down-regulated DEMs were detected, respectively. There were 236 target genes for up-regulated DEMs and 400 target genes for those down-regulated DEMs. For up-regulated DEMs, the top 10 hub genes were KRAS, NRAS, CDC42, GDNF, SOS1, PIK3R3, GSK3B, IRS2, GNG12, and PRKCA; for down-regulated DEMs, the top 10 hub genes were NR3C1, PPARGC1A, SUMO1, MEF2C, FOXO3, PPP1CB, MAP2K1, RARA, RHOC, CDC23, and CREB3L2. Mir-584-5p-KRAS, mir-183-5p-NRAS, mir-4435-PIK3R3, and mir-4435-SOS1 were identified as four potential regulatory pathways by integrated analysis. Conclusions We have integrated differential expression data to reveal putative genes and detected four potential miRNA-target gene pathways through bioinformatics analysis that represent new mediators of abnormal gene expression and promising therapeutic targets in OA.
format	article
author	Ying Jiang Yi Shen Liyan Ding Shengli Xia Liying Jiang
author_facet	Ying Jiang Yi Shen Liyan Ding Shengli Xia Liying Jiang
author_sort	Ying Jiang
title	Identification of transcription factors and construction of a novel miRNA regulatory network in primary osteoarthritis by integrated analysis
title_short	Identification of transcription factors and construction of a novel miRNA regulatory network in primary osteoarthritis by integrated analysis
title_full	Identification of transcription factors and construction of a novel miRNA regulatory network in primary osteoarthritis by integrated analysis
title_fullStr	Identification of transcription factors and construction of a novel miRNA regulatory network in primary osteoarthritis by integrated analysis
title_full_unstemmed	Identification of transcription factors and construction of a novel miRNA regulatory network in primary osteoarthritis by integrated analysis
title_sort	identification of transcription factors and construction of a novel mirna regulatory network in primary osteoarthritis by integrated analysis
publisher	BMC
publishDate	2021
url	https://doaj.org/article/3d9da812ff2a4031af6c48f78395e6be
work_keys_str_mv	AT yingjiang identificationoftranscriptionfactorsandconstructionofanovelmirnaregulatorynetworkinprimaryosteoarthritisbyintegratedanalysis AT yishen identificationoftranscriptionfactorsandconstructionofanovelmirnaregulatorynetworkinprimaryosteoarthritisbyintegratedanalysis AT liyanding identificationoftranscriptionfactorsandconstructionofanovelmirnaregulatorynetworkinprimaryosteoarthritisbyintegratedanalysis AT shenglixia identificationoftranscriptionfactorsandconstructionofanovelmirnaregulatorynetworkinprimaryosteoarthritisbyintegratedanalysis AT liyingjiang identificationoftranscriptionfactorsandconstructionofanovelmirnaregulatorynetworkinprimaryosteoarthritisbyintegratedanalysis
_version_	1718372069739069440

Identification of transcription factors and construction of a novel miRNA regulatory network in primary osteoarthritis by integrated analysis

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