Identification of IncRNA and mRNA Biomarkers in Osteoarthritic Degenerative Meniscus by Weighted Gene Coexpression Network and Competing Endogenous RNA Network Analysis
BIOMED RESEARCH INTERNATIONAL(2020)
Abstract
Background. Long noncoding RNAs (IncRNAs) play a crucial role in varieties of biological processes. This study is aimed at investigating meniscal degeneration-specific IncRNAs and mRNAs and their related networks in knee osteoarthritis (KOA). Methods. The dataset GSE98918, which included 24 meniscus samples and related clinical data, was downloaded from the Gene Expression Omnibus database. The differentially expressed IncRNAs and mRNAs in the meniscus between KOA and control groups were identified. Based on the enriched differentially expressed IncRNAs and mRNAs, we constructed the coexpression network using WGCNA (weighted correlation network analysis) and identified the critical module related to KOA. For mRNAs in the key module, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were carried out using the DAVID database. A competing endogenous RNA network (ceRNA) based on the screened mRNAs, IncRNAs, and related miRNAs was constructed to reveal presumptive biomarkers further. Finally, the hub IncRNAs and mRNAs were screened, and the diagnostic value was evaluated using a receiver operating characteristic (ROC) curve. Hub mRNAs were validated using the dataset GSE113825. Results. We screened 208 significantly differentially expressed IncRNAs and mRNAs in menisci between the KOA and non-KOA samples, which were enriched in sixteen modules using WGCNA, especially the green module. Co-expression network based on the enriched differentially expressed IncRNAs and mRNAs in the green module uncovered 5 IncRNAs and 56 mRNAs. The IncRNA-miRNA-mRNA ceRNA network revealed that Inc-HLA-DQA1-5, Inc-RP11-127H5.1.1-1, Inc-RTN2-1, IGFBP4 (insulin-like growth factor binding protein 4), and KLF2 (Kruppel-like factor 2) were significantly correlated with the meniscus degeneration of KOA. ROC curve analysis revealed that these hub IncRNAs and mRNAs showed excellent diagnostic value for KOA. Conclusions. These hub IncRNAs and mRNAs were potential prognostic biomarkers for the meniscus degeneration of KOA. Further studies are required to validate these new biomarkers and better understand the pathological process of the meniscus degeneration of KOA.
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Key words
Long Noncoding RNAs
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