Identification of lncRNA and mRNA Biomarkers in Osteoarthritic Degenerative Meniscus by Weighted Gene Coexpression Network and Competing Endogenous RNA Network Analysis.

BACKGROUND: Long noncoding RNAs (lncRNAs) play a crucial role in varieties of biological processes. This study is aimed at investigating meniscal degeneration-specific lncRNAs 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 lncRNAs and mRNAs in the meniscus between KOA and control groups were identified. Based on the enriched differentially expressed lncRNAs 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, lncRNAs, and related miRNAs was constructed to reveal presumptive biomarkers further. Finally, the hub lncRNAs 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 lncRNAs and mRNAs in menisci between the KOA and non-KOA samples, which were enriched in sixteen modules using WGCNA, especially the green module. Coexpression network based on the enriched differentially expressed lncRNAs and mRNAs in the green module uncovered 5 lncRNAs and 56 mRNAs. The lncRNA-miRNA-mRNA ceRNA network revealed that lnc-HLA-DQA1-5, lnc-RP11-127H5.1.1-1, lnc-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 lncRNAs and mRNAs showed excellent diagnostic value for KOA. CONCLUSIONS: These hub lncRNAs 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.

The potential roles of circular RNAs in osteonecrosis of the femoral head (Review).

Circular RNAs (circRNAs) are categorized as non­coding RNAs that, unlike widely known canonical linear RNAs, form a covalently closed continuous loop without 5' or 3' polarities, which enables them to resist digestion by RNA exonucleases. Although the functions of circRNAs remain largely unknown, accumulated evidence has demonstrated that circRNAs can act as microRNA sponges, which allows them to regulate numerous biological processes and disease mechanisms, including apoptosis, angiogenesis, invasion, metastasis and stem cell differentiation. Although research into circRNAs is in its infancy, studies have identified critical roles for circRNAs in the initiation and progression of disease. The present study delineated the characteristics and functions of circRNAs, and focused on the potential relationship between circRNAs and osteonecrosis of the femoral head (ONFH). CircRNAs represent a novel avenue for studying the mechanisms underlying ONFH as well as possible treatments.

miR-219 regulates liver cancer stem cell expansion via E-cadherin pathway.

Liver cancer stem cells contribute to tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liverCSCs is not fully understood yet. Here we show that miR-219 is upregulated in liver CSCs. Knockdown of miR-219 attenuates the self-renewal and tumorigenicity of liver CSCs. Conversely, miR-219 overexpressing enhances the self-renewal and tumorigenicity of liver CSCs.Mechanistically,miR-219 downregulates E-cadherin via itsmRNA 3'UTR in liver CSCs. The correlation between miR-219 and E-cadherin is validated in human HCC tissues. Furthermore, the miR-219 expression determines the responses of hepatoma cells to sorafenib treatment. Our findings indicate that miR-219 plays a critical role in liver CSCs expansion and sorafenib response, rendering miR-219 as an optimal target for the prevention and intervention of HCC.Abbreviations: HCC: Hepatocellular carcinoma; CSCs: cancer stem cells; DMEM: Dulbecco's modified Eagle's medium; FBS: fetal bovine serum; OS: overall survival.