Role of BIRC5 Up-Regulation Following HIF-1 Suppression in the Glioma Cells

Objective: The study was aimed to investigate role of HIF-1 alpha in regulating cell proliferation and the genes potentially regulated by HIF-1 alpha in gliomas. Methods: Short-hairpin RNA (siRNA) interference was introduced to inhibit HIF-1 alpha expression in the human glioma U251 cell line. Microarray, DEG, gene ontology (GO) analysis and gene interaction network was conducted to gain a comprehensive understanding of HIF-1 alpha in human glioma cells. Results: The expression of HIF-1 alpha was significantly suppressed by HIF-1 alpha siRNA transfection in the glioma cells. Proliferation of the glioma cells lacking HIF-1 alpha was significantly reduced. Furthermore, suppression of HIF-1 alpha resulted in significant up-regulation of 299 genes and down-regulation of 365 genes. These significantly altered genes participated in the signaling pathways in cancer, focal adhesion, terpenoid backbone biosynthesis, and renal cell carcinoma, as well as in many metabolic processes. Among the top 25 cancer associated genes, BIRC5 (survivin-1), ITGA2, and RALB were significantly up-regulated, particularly BIRC5. Conclusion: Suppression of HIF-1 alpha in human glioma cells remarkably augmented BIRC5 expression, suggesting that HIF-1 alpha may play a critical role in the tumorigenicity of glioblastoma through regulating BIRC5 gene expression.