Bioinformatics analysis of novel transcription factors and related differentially regulated modules in non-union skeletal fractures

OBJECTIVE: This study aimed to further clarify the underlying pathomechanism of non-union skeletal fractures. METHODS: Gene expression profile dataset GSE494 obtained from six non-union skeletal fracture and six normal samples was downloaded from the Gene Expression Omnibus database. Overlapping genes in at least two platforms were analyzed, and differentially expressed genes (DEGs) between normal and disease groups were screened. Transcriptional regulatory relationships and differentially regulated modules of various transcription factors (TFs) were determined. Differentially regulated modules with unknown functions were subjected to functional enrichment analysis. RESULTS: Overall, 4,252 overlapping genes in at least two platforms and 77 DEGs, including 31 up and 46 downregulated genes, were obtained. Overall, 64,623 transcriptional regulatory relationships, including 49 TFs and 3,900 target genes, and 9 significant modules for differential regulation were identified. Three modules with unknown functions regulated by TFs, including zinc finger, ZZ-type containing 3 (ZZZ3), nuclear TF Y, alpha (NFYA), and POU class 2 homeobox 2 (POU2F2), were identified. Enriched GO-BP terms of NFYA and POU2F2 modules included cell adhesion and related terms and those of ZZ3 included cell cycle, cell proliferation, and associated terms. CONCLUSION: Three TFs, including ZZZ3, POU2F2, and NFYA, and their regulated modules may have important effects on non-union skeletal fractures. Cell proliferation may be related with ZZZ3; cell adhesion and its similar process may be related with POU2F2 and NFYA.