Identification and integrated analysis of differentially expressed lncRNAs and circRNAs reveal the potential ceRNA networks during PDLSC osteogenic differentiation

Abstract

BackgroundResearchers have been exploring the molecular mechanisms underlying the control of periodontal ligament stem cell (PDLSC) osteogenic differentiation. Recently, long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) were shown to function as competitive endogenous RNAs (ceRNAs) to regulate the effect of microRNAs (miRNAs) on their target genes during cell differentiation. However, comprehensive identification and integrated analysis of lncRNAs and circRNAs acting as ceRNAs during PDLSC osteogenic differentiation have not been performed.ResultsPDLSCs were derived from healthy human periodontal ligament and cultured separately with osteogenic induction and normal media for 7 days. Cultured PDLSCs were positive for STRO-1 and CD146 and negative for CD31 and CD45. Osteo-induced PDLSCs showed increased ALP (alkaline phosphatase) activity and up-regulated expression levels of the osteogenesis-related markers ALP, Runt-related transcription factor 2 and osteocalcin. Then, a total of 960 lncRNAs and 1456 circRNAs were found to be differentially expressed by RNA sequencing. The expression profiles of eight lncRNAs and eight circRNAs were measured with quantitative real-time polymerase chain reaction and were shown to agree with the RNA-seq results. Furthermore, the potential functions of lncRNAs and circRNAs as ceRNAs were predicted based on miRanda and were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. In total, 147 lncRNAs and 1382 circRNAs were predicted to combine with 148 common miRNAs and compete for miRNA binding sites with 744 messenger RNAs. These mRNAs were predicted to significantly participate in osteoblast differentiation, the MAPK pathway, the Wnt pathway and the signaling pathways regulating pluripotency of stem cells. Among them, lncRNAs coded as TCONS_00212979 and TCONS_00212984, as well as circRNA BANP and circRNA ITCH, might interact with miRNA34a and miRNA146a to regulate PDLSC osteogenic differentiation via the MAPK pathway.ConclusionsThis study comprehensively identified lncRNAs/circRNAs and first integrated their potential ceRNA function during PDLSC osteogenic differentiation. These findings suggest that specific lncRNAs and circRNAs might function as ceRNAs to promote PDLSC osteogenic differentiation and periodontal regeneration.Electronic supplementary materialThe online version of this article (10.1186/s12863-017-0569-4) contains supplementary material, which is available to authorized users.

LncRNA‐PCAT1 targeting miR‐145‐5p promotes TLR4‐associated osteogenic differentiation of adipose‐derived stem cells

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CircRUNX2 through has‐miR‐203 regulates RUNX2 to prevent osteoporosis

“…It was predicted that circRNAs would combine with miRNA and compete for the binding sites on the miRNA with mRNAs . CircRNAs expression would alter the mRNA expression by targeting miRNAs that were binding to the mRNAs chosen.…”

The Long Noncoding RNA 150Rik Promotes Mesangial Cell Proliferation via miR-451/IGF1R/p38 MAPK Signaling in Diabetic Nephropathy

“…If they are located in the nucleus, they are mainly involved in the process of transcription and chromatin remodelling; when they are located in the cytoplasm, they principally participate in post-transcriptional gene regulation by forming complexes with specific proteins or acting as ceRNAs [41,42]. Since ceRNAs are important regulators between lncRNAs and microRNAs [43][44][45][46][47], we focused on the ceRNA mechanism of 150Rik and miR-451 in this study. We found that miR-451 is directly targeted by lncRNA 150Rik and IGF1R is the target gene of miR-451.…”