Study on the regulatory mechanism of AURKB in the apoptosis process of colorectal cancer cells induced by oxidative stress

Objective: To investigate the effect and mechanism of Aurora kinase B(AURKB) in mediating apoptosis by regulating PCNA and inducing oxidative stress in colorectal cancer(CRC). Methods: Combining public databases,clinical CRC and adjacent normal tissue specimens,the expression level of AURKB in CRC was detected by immunohistochemistry and Western blotting,and the relationship between it and the clinicopathological information of patients was analyzed and evaluated.The diagnostic value of AURKB for CRC patients was analyzed using the ROC curve,and the influence of AURKB on the prognosis of CRC patients was analyzed using the K-M curve.Combined with the follow-up data of patients,the prognosis value of CRC patients was evaluated.Based on CRC cells overexpressing AURKB and treated with the AURKB inhibitor AZD1152,the intracellular reactive oxygen species levels were determined,and the apoptosis experiments were conducted.The cells were divided into the DMSO group and AZD1152 group.Western blotting was used to detect the expressions of apoptosis-related proteins BAX and Bcl-2. Results: The expression level of AURKB in CRC was significantly higher than that in adjacent tissues(P<0.01).The K-M survival curve showed that the high expression of AURKB was significantly negatively correlated with the prognosis of CRC patients(P<0.01).The AURKB inhibitor AZD1152 could promote the production of reactive oxygen species in CRC tissues,and this promoting effect could be blocked by the reactive oxygen species inhibitor NAC.AZD1152 could also promote the apoptosis of CRC cells,and be blocked by AZD1152 as well.Bioinformatics analysis revealed that the AURKB was mainly enriched in the DNA damage repair pathway in CRC tissues,and the protein-protein interaction network indicated that PCNA had the highest correlation,suggesting that AURKB might regulate the malignant behavior of CRC cells by regulating PCNA. Conclusions: AURKB may be involved in the malignant biological behavior of CRC cells by regulating PCNA-mediated DNA oxidative damage.