Characterization of Dysregulated lncRNA-Associated ceRNA Network Reveals Novel lncRNAs With ceRNA Activity as Epigenetic Diagnostic Biomarkers for Osteoporosis Risk

The altered expression of long non-coding RNAs (lncRNAs) has been implicated in the development and human diseases. However, functional roles and regulatory mechanisms of lncRNA as competing endogenous RNAs (ceRNAs) in osteoporosis, and their potential clinical implication for osteoporosis risk are largely unexplored. In this study, we performed integrated analysis for paired expression profiles and regulatory relationships of dysregulated lncRNAs, mRNAs and miRNAs based on “ceRNA hypothesis”, and constructed an osteoporosis-related dysregulated miRNA-mediated lncRNA-mRNA ceRNA network (DysCeNet) composing of 105 nodes (including 8 miRNAs, 24 mRNAs, and 73 lncRNAs) and 515 edges. Functional analysis suggested that the DysCeNet was involved in known osteoporosis or bone metabolism-related biological progression and pathways. Then we performed random forest-based feature selection for 73 lncRNAs with ceRNA activity and identified 25 of 73 lncRNAs with ceRNA activity as potential diagnostic biomarkers. A random forest-based classifier composed of 25 lncRNA biomarkers (RF-25lncRNA) was developed for predicting osteoporosis risk. Performance evaluation with the leave-one-out cross-validation procedure showed that the RF-25lncRNA achieved well performance in distinguishing high and low BMD subjects in different osteoporosis datasets. Our study for the first time revealed a global view of lncRNA-associated ceRNA regulation in osteoporosis and provided novel lncRNAs with ceRNA activity as candidate epigenetic diagnostic biomarkers for early detection of osteoporosis risk.