An lncRNA-miRNA-mRNA ceRNA network for adipocyte differentiation from human adipose-derived stem cells

Human adipose tissue-derived stromal stem cells (HASCs) represent a promising regenerative resource for breast reconstruction and augmentation. However, the mechanisms involved in inducing its adipogenic differentiation remain to be fully elucidated. The present study aimed to comprehensively investigate the expression changes in mRNAs, microRNAs (miRNAs) and long non-coding (lnc)RNAs during the adipogenic differentiation of HASCs, and screen crucial lncRNA-miRNA-mRNA interaction axes using microarray datasets GSE57593, GSE25715 and GSE61302 collected from the Gene Expression Omnibus database. Following pretreatment, differentially expressed genes (DEGs), miRNAs (DE-miRNAs) or lncRNAs (DE-lncRNAs) between undifferentiated and differentiated HASCs were identified using the Linear Models for Microarray data method. A protein-protein interaction (PPI) network was constructed for the DEGs based on protein databases, followed by module analysis. The ‘lncRNA-miRNA-mRNA’ competing endogenous RNA (ceRNA) network was constructed based on the interactions between miRNAs and mRNAs, lncRNAs and miRNAs predicted by the miRWalk and lnCeDB databases. The underlying functions of mRNAs were predicted using the clusterProfiler package. In the present study, 905 DEGs, 36 DE-miRNAs and 577 DE-lncRNAs were screened between undifferentiated HASCs and differentiated adipocyte cells. PPI network analysis demonstrated that LEP may be a hub gene, which was also enriched in significant module 5. LEP was predicted to be involved in the Janus kinase-signal transducer and activator of transcription signaling pathway, and the regulation of inflammatory response. The upregulation of LEP was regulated by downregulated hsa-miRNA (miR)-130b-5p and hsa-miR-23a-5p (or hsa-miR-302d-3p). These miRNAs also respectively interacted with RP11-552F3.9 (or RP11-15A1.7), ultimately forming the ceRNA axes. In conclusion, the present study revealed that the RP11-552F3.9 (RP11-15A1.7)-hsa-miR-130b-5p/hsa-miR-23a-5p (hsa-miR-302d-3p)-LEP interaction axes may be crucial for inducing the adipogenic differentiation of HASCs via involvement in inflammation.