Abnormal sub-pathways competitively regulated by lncRNAs contribute to postmenopausal osteoporosis

Abnormal sub-pathways competitively regulated by long non-coding RNAs (lncRNAs) for postmenopausal osteoporosis (PO) based on integration of lncRNA-mRNA expression data and pathway network topologies were investigated. Interesting lncRNA-mRNA pairs were selected by Pearsons correlation coefficient (PCC) algorithm on the basis of lncRNA-miRNA and miRNA-mRNA interactions and gene expression profiles. Then, lncRNAs in interesting pairs were embedded into pathway graphs as signature nodes by linking to their regulated-mRNAs, and lncRNA competitively regulated pathways (LCRPs) were gained for PO patients. Moreover, sub-pathways were detected dependent on the shortest distance similarity and the pathway topology. The abnormal sub-pathways were determined utilizing the Wallenius approximation methods through evaluating the statistical significance of sub-pathways. In total 75 interesting lncRNA-mRNA pairs (representing 17 lncRNAs and 74 mRNAs) were identified. Subsequently, 42 LCRPs were extracted from pathway graphs by signature lncRNA regulated mRNAs. Moreover, 14 abnormal sub-pathways with P<0.05 were obtained between PO patients and controls, such as sub-pathways of PI3K-Akt signaling pathway and long-term potentiation. This finding may facilitate understanding the molecular mechanism of PO, and point a new direction to identify potential biomarkers for treatment and prevention of the disease.