Identification of aberrantly expressed long non-coding RNAs in postmenopausal osteoporosis

Abstract

Postmenopausal osteoporosis (PMOP) is a common skeletal disorder in postmenopausal women. The present study aimed to identify the key long non-coding RNAs (lncRNAs) in PMOP through RNA sequencing. RNA sequencing was performed to obtain the expression profile of lncRNAs and mRNAs in blood samples of patients with PMOP and normal controls (NCs). Following the identification of differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs), the DElncRNA-DEmRNA co-expression network was constructed. A search was performed for the DEGs transcribed within a 100-kb window upstream or downstream of DElncRNAs, which served as nearby DEmRNAs of DElncRNAs. Functional annotation of the DEmRNAs co-expressed with DElncRNAs was performed. The GSE56815 dataset was used to verify the expression of selected DEmRNAs and DElncRNAs. Three blood samples from patients with PMOP and two blood samples from NCs were used for RNA sequencing. Compared with the NC group, a total of 185 DEmRNAs and 51 DElncRNAs were obtained in PMOP. A total of 3,057 co-expression DElncRNA-DEmRNA pairs and 97 DElncRNA-nearby DEmRNA pairs were obtained. Six DEmRNAs [diacylglycerol O-acyltransferase 2, potassium voltage-gated channel subfamily S member 1, peptidase inhibitor 3, secretory leukocyte peptidase inhibitor, galectin-related protein and alkaline phosphatase, liver/bone/kidney (ALPL)] were nearby co-expressed genes of four DElncRNAs, including LOC105376834, LOC101929866, LOC105374771 and LOC100506113. Three PMOP-associated DEmRNAs, including ALPL, suppressor of cytokine signaling 3 and adrenomedullin, were co-expressed with the hub DElncRNAs (LINC00963, LOC105378415, LOC105377067, HCG27, LOC101928143 and LINC01094) of the positively and negatively co-expressed DElncRNA-DEmRNA interaction network. The expression of selected DEmRNAs and DElncRNAs was consistent with the RNA-sequencing results. In conclusion, the present study identified the key DEmRNAs and DElncRNAs in PMOP, which may provide clues for understanding the mechanism and developing novel biomarkers for PMOP.

Long non-coding RNA MIR22HG promotes osteogenic differentiation of bone marrow mesenchymal stem cells via PTEN/ AKT pathway

“…Recent studies have reported that lncRNAs could act as key regulators of osteogenic differentiation and pathological processes of osteoporosis 28 . Fei et al reported that 51 lncRNAs were differentially expressed in patients with osteoporosis compared with healthy controls 29 . Shen et al showed that the expression of lncRNA HOTAIR in osteoporosis patients was significantly higher than that in normal people.…”

Down-regulation of FTX promotes the differentiation of osteoclasts in osteoporosis through the Notch1 signaling pathway by targeting miR-137

“…It was commonly known that lncRNAs and miRNAs could bind to each other and exert biological functions in multiple types of human cancers [5,9]. Firstly, our study from bioinformatics predicted the shared binding sites between FTX and miR-137.…”

Long Non-coding RNAs: A New Regulatory Code for Osteoporosis

“…Several lncRNAs are differentially expressed in patients with osteoporosis and have been involved in the pathogenesis of this disease; however, additional studies with replication cohorts and larger samples are needed to support these findings. Using high-throughput RNA sequencing, Fei et al ( 64 ) identified 51 lncRNAs that were differentially expressed in patients with PMOP compared with healthy controls. These lncRNAs, including LINC00963, LOC105376834, LOC101929866, LOC105374771, and LOC100506113, may contribute to the pathogenesis of PMOP by regulating the expression of nearby and co-expressed differentially expressed mRNAs and the pathway of osteoclast differentiation.…”