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

Content Provider	Springer Nature : BioMed Central
Author	Jiang, Ying Shen, Yi Ding, Liyan Xia, Shengli Jiang, Liying
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.
Related Links	https://bmcmusculoskeletdisord.biomedcentral.com/counter/pdf/10.1186/s12891-021-04894-2.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
ISSN	14712474
DOI	10.1186/s12891-021-04894-2
Journal	BMC Musculoskeletal Disorders
Issue Number	1
Volume Number	22
Language	English
Publisher	BioMed Central
Publisher Date	2021-12-02
Access Restriction	Open
Subject Keyword	Orthopedics Rehabilitation Rheumatology Sports Medicine Internal Medicine Epidemiology Osteoarthritis Circulating microRNAs RNA sequencing Bioinformatics analysis
Content Type	Text
Resource Type	Article
Subject	Orthopedics and Sports Medicine Rheumatology
Journal Impact Factor	2.2/2023
5-Year Journal Impact Factor	2.6/2023

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