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A Long Noncoding RNA (lncRNA)-Associated Competing Endogenous RNA (ceRNA) Network Identifies Eight lncRNA Biomarkers in Patients with Osteoarthritis of the Knee.

ABSTRACT: BACKGROUND Osteoarthritis (OA) of the knee is a common disease that is associated with chronic pain. This study aimed to identify and investigate the functional role of biomarkers associated with long noncoding RNA (lncRNA) in the progression of OA of the knee by lncRNA-associated competing endogenous RNA (ceRNA) integrated network analysis. MATERIAL AND METHODS High-quality microRNA (miRNA)-lncRNA and miRNA-mRNA interactions and lncRNA and mRNA expression profiles for patients with OA of the knee with mild and severe pain were obtained from the Gene Expression Omnibus (GEO) database (GSE99662). A three-step computational method was used to construct the lncRNA-associated ceRNA interaction network in OA by integrating miRNA-lncRNA/mRNA interactions and lncRNA/mRNA expression profiles in patients with OA with mild and severe pain. RESULTS A total of 1,870 dysregulated lncRNA-mRNA interactions were obtained in the lncRNA-associated ceRNA network in OA, including 476 gain and 1,394 loss interactions, covering 131 lncRNAs and 1,251 mRNAs. Characterization of the lncRNA-associated ceRNA network in OA indicated that lncRNAs had roles in the network. Further differential expression analysis identified eight lncRNA biomarkers, which could distinguish between patients with OA with mild pain and severe pain. These lncRNA-associated interactions showed significantly different co-expression patterns in samples from patients with OA of the knee associated with mild pain. CONCLUSIONS Integrated network analysis of lncRNA-associated ceRNA identified eight lncRNA molecular biomarkers associated with the progression of OA of the knee.

SUBMITTER: Chen Y

PROVIDER: S-EPMC6437717 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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A Long Noncoding RNA (lncRNA)-Associated Competing Endogenous RNA (ceRNA) Network Identifies Eight lncRNA Biomarkers in Patients with Osteoarthritis of the Knee.

Chen Yuxi Y Lin Yu Y Bai Ye Y Cheng Daolin D Bi Zhenggang Z

Medical science monitor : international medical journal of experimental and clinical research 20190320

BACKGROUND Osteoarthritis (OA) of the knee is a common disease that is associated with chronic pain. This study aimed to identify and investigate the functional role of biomarkers associated with long noncoding RNA (lncRNA) in the progression of OA of the knee by lncRNA-associated competing endogenous RNA (ceRNA) integrated network analysis. MATERIAL AND METHODS High-quality microRNA (miRNA)-lncRNA and miRNA-mRNA interactions and lncRNA and mRNA expression profiles for patients with OA of the kn ...[more]

PMID: 30890688

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Project description:BackgroundOsteoarthritis (OA) is one of the most common diseases in elderly people; however, the correlation between molecular alterations and the occurrence and progression of OA are still not well understood. We conducted this study to investigate the molecular changes in OA via the competing endogenous ribonucleic acid (ceRNA) network.MethodsWe downloaded the messenger RNA (mRNA) data set, GSE48556, the microRNA (miRNA) data set, GSE105027, and the long non-coding (lncRNA) data set, GSE126963 from the Gene Expression Omnibus (GEO) database, and examined the differentially expressed genes (DEGs) in these data sets. Further, we constructed a ceRNA network of the differentially expressed miRNAs, mRNAs, and lncRNAs. To determine the biological functions of the ceRNA network, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Finally, we conducted an immune cell infiltration analysisusing single-sample gene set enrichment analysis to examine the abundance of immune cells in healthy and OA patients, and compared the infiltration of 28 immune cells between the healthy and OA samples. We also analyzed the relationship between the abundance of immune cells and mRNA expression levels in the ceRNA network.ResultsUltimately hsa-mir-425-3p, dual specificity phosphatase 1, and 24 lncRNAs were identified in the ceRNA network. The functional enrichment analyses showed that these lncRNAs, miRNAs, and mRNAs are involved in various significant biological process, such as the regulation of leukocyte migration, Mitogen-Activated Protein (MAP) kinase tyrosine/serine/threonine phosphatase activity, the interleukin-17 signaling pathway, the tumor necrosis factor signaling pathway, and osteoclast differentiation, and can also have a strong effect on immune cell infiltration.ConclusionsThe dual-specificity phosphatase 1-specific ceRNA network can be used as a diagnostic tool to assess the progression of OA patients.

Dataset Information

A Long Noncoding RNA (lncRNA)-Associated Competing Endogenous RNA (ceRNA) Network Identifies Eight lncRNA Biomarkers in Patients with Osteoarthritis of the Knee.

Publications

A Long Noncoding RNA (lncRNA)-Associated Competing Endogenous RNA (ceRNA) Network Identifies Eight lncRNA Biomarkers in Patients with Osteoarthritis of the Knee.

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