Identification of hypoxia-regulated angiogenic genes in colorectal cancer

Abstract

The tumour hypoxia would trigger the angiogenesis switch for survival, and increase the ability of cancer cells to invade and metastasis. However, hypoxia regulated genes that invovled in angiogenesis in colorectal cancer (CRC) have not been explored in detail. The aim of this study was to explore angiogenic genes under hypoxia condition in CRC. Here, we found that endothelial cells tube formation and cancer cells invasion ability were promoted even under chronic hypoxia condition (72 h) in colon adenocarcinoma HCT-116 cells. Then, we explored the differentially expressed genes (DEGs) under chronic hypoxia condition by microarray from Gene Expression Omnibus (GEO) database. Subsequent bioinformatic analysis identified 17 genes that invovled in angiogenesis, blood vessel development, blood vessel morphgensis, vascular development. of these genes, VEGF-A, Smad7, Jun, IL-8, CXCR-4, PDGF-A, TGF-A, ANGPTL-4 expression levels up-regulated under hypoxia condition. Additionally, the gene expression level in acute hypoxia (24 h) was significantly higher than chronic condition (72 h). Finally, knockdown of hypoxia inducible factor (HIF-1α) by shRNA reversed the role of Smad7, CXCR-4, PDGF-A, TGF-A and ANGPTL-4 overexpression in HCT-116 cells, these findings provide the potential angiogenic targets for the treatment of colorectal cancer.

Keywords: Angiogenesis; Colorectal cancer; Gene-expression profile; Hypoxia.