Abstract

BackgroundInjection of adipose-derived stem cells (ASCs) is a promising treatment for facial contour deformities. However, its treatment mechanisms remain largely unknown. The study aimed to explain the molecular mechanisms of adipogenic differentiation from ASCs based on the roles of long noncoding RNAs (lncRNAs).MethodsDatasets of mRNA–lncRNA (GSE113253) and miRNA (GSE72429) expression profiling were collected from Gene Expression Omnibus database. The differentially expressed genes (DEGs), lncRNAs (DELs) and miRNAs (DEMs) between undifferentiated and adipocyte differentiated human ASCs were identified using the Linear Models for Microarray Data method. DELs related co-expression and competing endogenous RNA (ceRNA) networks were constructed. Protein–protein interaction (PPI) analysis was performed to screen crucial target genes.ResultsA total of 748 DEGs, 17 DELs and 51 DEMs were identified. A total of 13 DELs and 279 DEGs with Pearson correlation coefficients > 0.9 and p-value < 0.01 were selected to construct the co-expression network. A total of 151 interaction pairs among 112 nodes (10 DEMs; eight DELs; 94 DEGs) were obtained to construct the ceRNA network. By comparing the lncRNAs and mRNAs in two networks, five lncRNAs (SNHG9, LINC02202, UBAC2-AS1, PTCSC3 and myocardial infarction associated transcript (MIAT)) and 32 genes (i.e., such as phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), protein tyrosine phosphatase receptor type B (PTPRB)) were found to be shared. PPI analysis demonstrated PIK3R1 , forkhead box O1 (FOXO1; a transcription factor) and estrogen receptor 1 (ESR1) were hub genes, which could be regulated by the miRNAs that interacted with the above five lncRNAs, such as LINC02202-miR-136-5p-PIK3R1, LINC02202-miR-381-3p-FOXO1 and MIAT-miR-18a-5p-ESR1. LINC02202 also could directly co-express with PIK3R1. Furthermore, PTPRB was predicted to be modulated by co-expression with LINC01119.ConclusionMIAT, LINC02202 and LINC01119 may be potentially important, new lncRNAs associated with adipogenic differentiation of ASCs. They may be involved in adipogenesis by acting as a ceRNA or co-expressing with their targets.

Highlights

  • Autologous adipose tissue grafting has been a widely accepted surgical tool for anti-aging cosmetics (Charles-De-Sá et al, 2015) and reconstructive restoration of various congenital or acquired facial soft tissue deformities (Bashir et al, 2018)

  • Differential expression analysis Due to the fact that fewer differentially expressed genes (DEGs), DELs and DEMs were identified if adjusted p-value was defined as the statistical threshold; genes, long noncoding RNAs (lncRNAs) and miRNAs were believed to be differentially expressed in this study when their |log2fold change (FC)| was more than 1 and p-value was less than 0.05

  • 121 DEGs (such as forkhead box O1 (FOXO1), protein tyrosine phosphatase receptor type B (PTPRB)) and two DELs (SH3RF3-AS1, LINC01119) had adjusted p-value < 0.05, indicating they were especially crucial for adipogenic differentiation

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Summary

Introduction

Autologous adipose tissue grafting has been a widely accepted surgical tool for anti-aging cosmetics (Charles-De-Sá et al, 2015) and reconstructive restoration of various congenital or acquired facial soft tissue deformities (Bashir et al, 2018). Conventional fat grafting procedure needs to be repeated multiple times to achieve satisfactory results (Bashir et al, 2018), which may be associated with the low graft survival rate and poor revascularization (Ma et al, 2015) To overcome these two limitations, recent scholars propose to combine with additional autologous adipose-derived stem cells (ASCs) which have the ability to differentiate into mature adipocytes to supplement apoptotic cells and secrete angiogenic growth factors to enhance angiogenesis (Bashir et al, 2018; Kotaro et al, 2008; Philips, Marra & Rubin, 2014). They may be involved in adipogenesis by acting as a ceRNA or co-expressing with their targets

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Conclusion

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