Long Noncoding RNA Sponges miR-454 to Promote Osteogenic Differentiation in Maxillary Sinus Membrane Stem Cells

Implant Dent. 2017 Apr;26(2):178-186. doi: 10.1097/ID.0000000000000569.

Abstract

Objective: Although increasing evidence has shown that long noncoding RNAs (lncRNAs) play an important regulatory role in pluripotency and differentiation of mesenchymal stem cells, little is known about the role of lncRNA in maxillary sinus membrane stem cells (MSMSCs). The goal of this study was to investigate the expression profile and function of lncRNAs on osteogenic differentiation of MSMSCs.

Materials and methods: By using lncRNA microarray, we identify a novel osteogenesis differentiation-related lncRNA of MSMSCs (lncRNA-MODR). The functional role of lncRNA-MODR in regulating osteogenesis was evaluated by quantitative real-time polymerase chain reaction, western blot, and alizarin red staining. Bioinformatic analyses of the predicted target genes (gene ontology, pathway, and network analysis) were applied for further study of lncRNA-MODR.

Results: We show that lncRNA-MODR is gradually upregulated during osteogenic differentiation. lncRNA-MODR overexpression upregulated, whereas lncRNA-MODR silencing decreased the expression of the osteogenic key marker, runt-related transcription factor 2 (RUNX2). In-depth analyses showed that lncRNA-MODR acts as a molecular sponge for microRNA-454 (miR-454) and that prevents RUNX2 from mi-454-mediated suppression.

Conclusion: The lncRNAs act as a competing endogenous RNA to sequester microRNA-454 (miR-454), leading to heightened RUNX2 expression and thus promotes osteogenesis of MSMSCs.

MeSH terms

  • Blotting, Western
  • Cell Differentiation / drug effects
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Humans
  • Maxillary Sinus / cytology
  • Maxillary Sinus / drug effects*
  • MicroRNAs / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Osteogenesis / physiology*
  • RNA, Long Noncoding / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Stem Cells / drug effects*
  • Stem Cells / physiology

Substances

  • Core Binding Factor Alpha 1 Subunit
  • MIRN454 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RUNX2 protein, human