Identification of hypoxia-regulated angiogenic genes in colorectal cancer

• Published in: Biochemical and biophysical research communications Vol. 493; no. 1; pp. 461 - 467
• Main Authors: Zong, Shaoqi, Li, Wen, Li, Hongjia, Han, Susu, liu, Shanshan, Shi, Qi, Hou, Fenggang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.11.2017
• Subjects: Acute Disease; Angiogenesis; Angiogenic Proteins - metabolism; Chronic Disease; Colorectal cancer; Colorectal Neoplasms - complications; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Gene Expression Profiling; Gene-expression profile; Genes, Neoplasm; Humans; Hypoxia; Neoplasm Invasiveness; Neoplasm Proteins - metabolism; Neovascularization, Pathologic - complications; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Tumor Hypoxia; Angiogenesis; Hypoxia; Gene-expression profile; Colorectal cancer
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.08.169

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. •Chronic hypoixa promoted cancer cell invasion and angiogenesis in colorectal cancer.•Identification and validation of 8 angiogenic genes under hypoxia condition based on bioinformatic analysis.•The expression level of angiogenic genes in acute hypoxia was significantly higher than chronic hypoxia condition.•HIF-1αis required for the regulation of Smad7, CXCR-4, PDGF-A, TGF-A and ANGPTL-4 transcription in response to hypoxia.