氯化两面针碱潜在靶标极光激酶A在结直肠癌组织中的临床病理价值

The Clinicopathological Value of Aurora Kinase A Which is a Therapeutic Target of Nitidine Chloride in Colorectal Cancer Tissues

目的:探究极光激酶A(AURKA)在结直肠癌中的临床病理价值。方法:通过分子对接探究AURKA与氯化两面针碱(NC)结合强度。结合免疫组织化学数据和全球高通量数据集分析结直肠癌中AURKA蛋白和mRNA表达水平,计算标准平均偏差(SMD)和总结受试者操作特征(sROC),以探讨AURKA在结直肠癌和放疗抵抗中综合表达水平,利用CRISPR敲除筛选以及体外敲低AURKA后的基因芯片数据,分析AURKA促癌潜在分子机制。结果:AURKA与NC结合能为-10kcal/mol, AURKA蛋白在结直肠癌中表达上调,mRNA在2 511个结直肠癌样本和41个放疗抵抗样本中表达上调,显示结直肠癌中SMD为2.07,放疗抵抗中SMD为0.73。敲低AURKA在结直肠癌LS123细胞系中生长抑制最显著。体外敲低AURKA mRNA后基因主要富集于肌动蛋白、线粒体膜、细胞周期检查点通路。结论:在结直肠癌中,AURKA是潜在的NC和放疗增敏靶点,下调AURKA有望用于临床治疗。

Objective:To investigate the clinicopathological value of Aurora kinase A(AURKA)in colorectal cancer.Methods:The bonding strength of AURKA with niamnidine chloride(NC)was studied by molecular docking.The protein and mRNA expression levels of AURKA in colorectal cancer were analyzed by immunohistochemical data and the global high-throughput sequencing datasets.The standardized mean difference(SMD)and summary receiver operating characteristics(sROC)were calculated to comprehensively discuss the levels of AURKA in colorectal cancer and radiotherapy resistance.The potential molecular mechanism of AURKA for cancer was further analyzed using CRISPR knockout screens data and Genechip data after AURKA knock-down in vitro.Results:The binding energy of AURKA and NC was-10kcal/mol.The expression of AURKA protein was up-regulated in colorectal cancer,and mRNA was up-regulated in 2511 colorectal cancer samples(the SMD was 2.07)and 41 radiotherapy resistance samples(the SMD was 0.73).Knocking down AURKA showed the most significant growth inhibition in the LS123 cell line of colorectal cancer.Moreover the genechip data revealed that the genes were mainly enriched in pathways of actin binding,mitochondrial outer membrane,and cell cycle checkpoints after AURKA mRNA knock-down in vitro.Conclusion:AURKA is the potential target of NC and radiotherapy in colorectal cancer.AURKA down-regulation is expected to be used for clinical treatment.