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    AURKB在氧化应激诱导的结直肠癌细胞凋亡过程中的调控机制

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

      摘要
    • 摘要:
      目的 探讨极光激酶B(AURKB)通过介导增殖细胞核抗原(PCNA)调控结直肠癌(CRC)的氧化应激从而导致CRC细胞凋亡的作用及其机制。
      方法 结合公共数据库和临床CRC及癌旁正常组织标本，采用免疫组织化学法和Western blotting法检测AURKB在CRC中表达水平，并分析评价其与病人临床病理信息之间关系；ROC曲线分析AURKB对CRC病人诊断价值；K-M曲线分析AURKB对CRC病人预后的影响；结合病人随访资料，分析其在CRC病人预后评价中的价值。以过表达AURKB和使用AURKB抑制剂AZD1152处理的CRC细胞为基础，对细胞内活性氧水平进行测定，并进行细胞凋亡实验。将细胞分为DMSO组和AZD1152组，Western blotting检测凋亡相关蛋白BAX、Bcl-2表达。
      结果 AURKB在CRC中表达水平明显高于癌旁组织(P < 0.01)。K-M生存曲线显示，AURKB高表达与CRC病人预后呈明显负相关关系(P < 0.01)。AURKB抑制剂AZD1152可以促进CRC组织中活性氧产生，且这种促进作用可以被活性氧抑制剂NAC所阻断。AZD1152同时也可促进CRC细胞凋亡，且同样可以被AZD1152所阻断。生物信息学分析显示，AURKB在CRC组织中主要富集在DNA损伤修复通路，且蛋白互作网络显示PCNA具有最高相关度，提示AURKB可能通过调控PCNA调控CRC细胞的恶性行为。
      结论 AURKB可能通过调控PCNA介导的DNA氧化损伤参与CRC细胞恶性生物学行为。

       

      Abstract:
      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.

       

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