Authors : Duan-Yi Zhao, Ming-Kai Chen, Cong-Qing Jiang, Bangoura Gassimou, Zhi-Su Liu and Zhuo Cao
Abstract: HIF-1α participates in the neovascularization of colorectal adenocarcinoma tumor and the development of tumor via regulating VEGF expression. NDRG1 was over expressed in the process of colorectal adenocarcinoma. Current studies demonstrate that hypoxia is a NDRG1-inducible factor and HIF-1α also has taken part in this process. The study was to investigate regulation relationship between HIF-1α and NDRG1 in the LS174T cells and the two proteins associated with human colorectal carcinoma Duke classification. Construct siRNA expressive carrier pSilence-2.1-U6-siRNA targeting Hypoxia-Inducible Factor-1α (HIF-1α), hypoxially cultured LS174T cells were transferred by liposome. HIF-1α and NDRG1 mRNA and protein expression level was analyzed by RT-PCR and Western blot. In addition, 62 cases of clinical tissue specimen of human colorectal carcinoma were collection to detect HIF-1 and NDRG1 expression level using ISH, IHC. HIF-1α gene expression was inhibited by siRNA at transcriptional and protein level in the LS174T cells under hypoxia conditions for 24 h. Meanwhile, NDRG1mRNA expression was also significantly suppressed. In colorectal adenocarcinoma organization, HIF-1α and NDRG1 positive expression was both significantly correlated with Dukes staging (p<0.05). Moreover, spearman correlation analysis displayed HIF-1α was correlated with NDRG1 (p<0.05). The over expression of HIF-1α and NDRG1 likely play pivotal roles in the development of colorectal gland adenoma canceration and colorectal adenocarcinoma.
Duan-Yi Zhao, Ming-Kai Chen, Cong-Qing Jiang, Bangoura Gassimou, Zhi-Su Liu and Zhuo Cao, 2012. The Regulatory Role of Colorectal Adenocarcinoma Hypoxia-Inducible Factor-1α in the Expression of N-myc Down-Stream Regulative Gene 1. Journal of Animal and Veterinary Advances, 11: 4121-4126.