Fig. 8. Mechanism diagram.

Our study demonstrated that CIRBP could promote BCa cells proliferation and migration both in vitro and in vivo. Furthermore, CIRBP could increase HIF-1α expression by binding to the 3′-UTR of HIF-1A mRNA transcripts and increasing its mRNA stability in BCa cell line. HIF-1α could activate transcription of many oncogenes, such as VEGF, C-MYC, and OCT4. Our results showed that PTGIS is a HIF-1α target gene, which could suppress BCa cells proliferation and migration, and overexpression of HIF-1A could suppress the expression of PTGIS in BCa cells by binding to HRE sequence (5′-ccACGTGc-3′) of the PTGIS promoter region. Moreover, methylation of PTGIS gene promoter may be an important reason why PTGIS expression is downregulated by HIF-1α. And DNA methylation is also an important reason for obvious downregulation of PTGIS in BCa