AIM: To investigate the roles and interactions of mutT homolog (MTH)-1 and hypoxia-inducible factor (HIF)-1á in human colorectal cancer (CRC).METHODS: The expression and distribution of HIF-1á and MTH-1 proteins were detected in human CRC tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). SW480 and HT-29 cells were exposed to normoxia or hypoxia. Protein and mRNA levels of HIF-1á and MTH-1 were analyzed by western blotting and qRT-PCR, respectively. In order to determine the effect of HIF-1á on the expression of MTH-1 and the amount of 8-oxo-deoxyguanosine triphosphate (dGTP) in SW480 and HT-29 cells, HIF-1á was silenced with small interfering RNA (siRNA). Growth studies were conducted on cells with HIF-1á inhibition using a xenograft tumor model. Finally, MTH-1 protein was detected by western blotting in vivo.RESULTS: High MTH-1 mRNA expression was detected in 64.2% of cases (54/84), and this was significantly correlated with tumor stage (P = 0.023) and size (P = 0.043). HIF-1á protein expression was correlated significantly with MTH-1 expression (R = 0.640; P < 0.01) in human CRC tissues. Hypoxic stress induced mRNA and protein expression of MTH-1 in SW480 and HT-29 cells. Inhibition of HIF-1á by siRNA decreased the expression of MTH-1 and led to the accumulation of 8-oxo-dGTP in SW480 and HT-29 cells. In the in vivo xenograft tumor model, expression of MTH-1 was decreased in the HIF-1á siRNA group, and the tumor volume was much smaller than that in the mock siRNA group.CONCLUSION: MTH-1 expression in CRC cells was upregulated via HIF-1á in response to hypoxic stress, emphasizing the crucial role of HIF-1á-induced MTH-1 in tumor growth.
Cell Hypoxia Cell Proliferation