2022, Vol. 26 ›› Issue (24): 3908-3913

Transcription factor-miRNA-mRNA network analysis of osteogenic differentiation of adipose-derived stem cells

Yu Chunbo, Li Dayu, Fan Fang, Li Changfu   

Abstract: BACKGROUND: Adipose stem cells have a wide range of sources and are easy to obtain. The changes in gene expression involved in the entry of human adipose tissue-derived stem cells into differentiated bone cells are mainly regulated by miRNA and transcription factor, but the specific molecular mechanisms that regulate the osteogenic differentiation of adipose stem cells and their potential transcription factor-miRNA-mRNA regulatory network have not yet been established.  
OBJECTIVE: To screen the differentially expressed genes, differentially expressed miRNAs and transcription factors during the osteogenic differentiation of adipose-derived stem cells, and to explore the potential target genes, miRNAs, transcription factors, and transcription factor-miRNA-mRNA regulatory network during the osteogenic differentiation of adipose-derived stem cells.
METHODS: GEO database was used to acquire three chips (GSE37329, GSE63754 two miRNA gene chips and GSE72429 one miRNA data chip) to screen differentially expressed genes and differential miRNAs. Differentially expressed genes were analyzed for PPI network, GO function, and KEGG signaling pathway. Differentially expressed genes were utilized to predict upstream miRNAs and differential miRNAs pre-transcription factors. Transcription factor-miRNA-mRNA network diagrams were constructed through Cytoscape 3.7.1 software.  
RESULTS AND CONCLUSION: Eighty-six differentially expressed genes (26 up-regulated genes, 60 down-regulated genes) and 16 differential miRNAs (10 up-regulated miRNAs, 6 down-regulated miRNAs) were screened out. There were 76.52% of protein interactions and co-expression and 8.69% of synergistic localization in the PPI network. GO function enrichment analysis was mainly related to the negative regulation of the classical Wnt signaling pathway and the negative regulation of cartilage development. The KEGG signaling pathway involved signaling pathways, such as tyrosine metabolism and fatty acid degradation. Differentially expressed genes predicted 11 381 miRNAs and differential miRNAs predicted 55 transcription factors. Transcription factor-miRNA-mRNA regulatory network was constructed. The key genes in the osteogenic differentiation of adipose-derived stem cells may be PODXL, SEMA3D, ADGRG6, LGR4, LPL, CADM3, GRIA1, GPM6B, RERG, APCDD1, and NRCAM. Important miRNAs were: hsa-miR-762, hsa-miR-502-3p, and hsa-miR-1275. The core transcription factors were CTCF, TAL1, STAT2, STAT1, and TCF3. The results show that the transcription factor-miRNA-mRNA regulatory network constructed through bioinformatics technology and database mining methods provides potential therapeutic targets for the in-depth study of osteogenic differentiation of adipose-derived stem cells.
Key words: adipose-derived stem cells, osteogenic differentiation, transcription factor, bioinformatics, miRNA, differentially expressed genes