锌指含髓样神经变形表皮生长因子结构域第8亚型作为糖皮质激素受体下游基因在前列腺癌组织的表达及临床意义

Expression and significance of Zinc finger MYND-type containing 8 in prostate cancer via the regulation of glucocorticoid receptor

目的 验证锌指含髓样神经变形表皮生长因子结构域第8亚型（ZMYND8）与糖皮质激素受体（GR）之间调控关系,探讨ZMYND8表达量与前列腺癌各临床病理特征之间的关系.方法通过软件预测及在敲除GR基因的前列腺癌细胞PC3中用Western blot实验方法检测ZMYND8表达量,分析GR与ZMYND8之间的关系,并在80例前列腺癌及非癌组织的组织芯片中使用免疫组织化学的方法,对ZMYND8蛋白表达量与前列腺癌各病理特征之间的关系进行分析.结果 ZMYND8 基因受GR基因调控,ZMYND8在癌组织及转移癌中表达上调（免疫组织化学评分：非癌组织为5.700±2.054,癌组织为7.340±2.163,P=0.001,转移癌组织为6.710±2.369,非转移癌组织为8.110±1.595,P=0.028）,差异有统计学意义.结论 ZMYND8的表达受上游基因GR的调控,ZMYND8基因在前列腺癌临床上表现为促癌基因.

Objective To identify Zinc finger MYND-type containing 8 （ZMYND8） as a direct target for glucocorticoid receptor （GR） and illustrate the correlations between ZMYND8 and clinical characteristics of prostate cancer.Methods Bioinformatics software and Western blotting were used to analyze the relationship between ZMYND8 and GR in GR-knock-out prostate cancer cells.In order to evaluated the correlation of ZMYND8 with clinical characteristics,immunohistochemistry was used to detect ZMYND8 protein in 80 cases of prostate cancer and benign prostate hyperplasia （BPH） tissues.Results ZMYND8 functioned as a cancer promoter via the regulation of GR,and the expression of ZMYND8 protein was significantly increased in prostate cancer and metastatic tumor tissue （immunoreactivity score： no cancer： 5.700±2.054,cancer： 7.340±2.163,P=0.001;metastatic cancer： 6.710±2.369,non-metastatic cancer： 8.110±1.595,P=0.028）.Conclusion Our study showed that ZMYND8 is regulated by GR,and ZMYND8 is a cancer promoter in prostate cancer.