Identification of functional lncRNAs based on competing endogenous RNA network in osteoblast differentiation

Abstract

Adult human mesenchymal stem cells have the potential to differentiate into osteoblast, which plays crucial roles in bone regeneration and repair. Some transcriptional factors (TFs), such as BMP-2 and RUNX2, have been demonstrated to control the differentiation processes. It is important to discover more key regulators in osteoblast differentiation. Recently, some studies found long noncoding RNAs (lncRNAs) participating in osteoblast differentiation, such as MALAT1, DANCR, and ANCR. In this study, we performed a network-based computational analysis to investigate the lncRNA-messenger RNA (mRNA) crosstalks via integrating microRNA (miRNA)-RNA interactions, gene coexpression, and protein-protein interactions.First, multiple topology analyses were performed to osteoblast-differentiationrelated lncRNA-mRNA network (ODLMN). Several lncRNAs with central topology structures were identified as key regulators. Results showed that these lncRNAs participated in osteoblast differentiation via phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase, and Ras signals. Previous studies have demonstrated that lncRNAs exert functions by involving in close modules. Second, after performing module searching in ODLMN, two functional modules were identified, which played crucial roles through involving in PI3K/protein kinase B, cyclic adenosine 3ʹ,5ʹ-monophosphate, and hypoxia-inducible factor 1 pathways. Third, a subset of core lncRNA-TF crosstalks that might form feedback loops to control the biological processes in osteoblast differentiation was identified. These core lncRNA-TF feedback loops showed more TF binding affinity than other lncRNAs.All these results can help us to uncover the molecular mechanism and provide new targets for bone regeneration and repair.

lncRNA IGHCγ1 Acts as a ceRNA to Regulate Macrophage Inflammation via the miR-6891-3p/TLR4 Axis in Osteoarthritis

“…As a kind of noncoding RNA, lncRNA can function as ceRNA and restrain miRNA by lncRNA-miRNA sponge in cancer, cardiovascular disease, and so on [25,26]. Several functional lncRNAs have been demonstrated to influence osteoblast differentiation and OA pathogenesis through lncRNA-miRNA-mRNA ceRNA mechanism [27][28][29][30]. Some lncRNAs can affect the degradation of the extracellular matrix of chondrocytes by functioning as ceRNAs of specific miRNAs and thus participate in the development and progression of OA, such as lncRNAs of HOTTIP, MEG3, and XIST [28,29,31].…”

“…Some lncRNAs can affect the degradation of the extracellular matrix of chondrocytes by functioning as ceRNAs of specific miRNAs and thus participate in the development and progression of OA, such as lncRNAs of HOTTIP, MEG3, and XIST [28,29,31]. Some lncRNAs have been well documented to regulate the differentiation of osteoblasts via the lncRNA-miRNA ceRNA network [27]. Besides, Fan et al have found that DANCR can regulate the progression of OA via targeting miR-577 through ceRNA mechanism [32].…”

Hypoxia preconditioning promotes mesenchymal stem cells survival and vascularization through the activation of MALAT1/miR-195/VEGFA axis

“…The lncRNA-associated competing endogenous RNA (ceRNA) network has attracted much attention recently [12,[32][33][34]. Series of records have proved that MALAT1 play a prominent role in cell proliferation, differentiation and angiogenesis by functioning as a ceRNA [40]. One latest study indicates that MALAT1 mediates proliferation and apoptosis of VSMCs by sponging miRNA-124-3p [41].…”

The Involvement of Long Non-Coding RNAs in Bone

“…Hong et al [71] investigated the lncRNA-mRNA crosstalk, by using computational analysis, to realize a network called "osteoblast-differentiation-associated lncRNA-mRNA network" (ODLMN). First, the authors identified lncRNAs and genes differentially expressed in osteogenic differentiation.…”