MeCP2在卵巢浆液性囊腺癌中的表达及意义

目的 探究甲基化CpG结合蛋白（Methyl-CpG-binding protein 2,MeCP2）表达对卵巢浆液性囊腺癌SKOV3细胞增殖的作用。方法 在TCGA数据库中获取卵巢浆液性囊腺癌患者组织的RNA测序数据与临床病理学信息,利用生物信息学方法分析MeCP2在健康者和卵巢浆液性囊腺癌患者中的表达及其与卵巢浆液性囊腺癌临床病理学分期、生存期的相关性;分别利用MTT实验、细胞克隆实验、细胞周期及细胞凋亡实验分析MeCP2表达对SKOV3细胞增殖的影响。基因集富集分析（Gene set enrichment analysis,GSEA）获取MeCP2表达调节的关键信号通路,利用Western blot进行相关蛋白的检测。结果 MeCP2在卵巢浆液性囊腺癌患者中的表达显著降低;MeCP2的表达与卵巢浆液性囊腺癌的病理学分期相关,而与组织学分级无关;生存期分析显示,MeCP2高表达患者的无病生存期显著长于低表达患者,而MeCP2的表达对于患者整体生存期、疾病特异性生存期、无进展间隔生存期没有影响;细胞功能实验显示过表达MeCP2能够抑制细胞增殖活性、细胞克隆形成能力及阻滞细胞周期G₁/S期的转化并诱导细胞发生凋亡。MeCP2表达调节的信号通路分析显示,MeCP2能够抑制ERBB信号通路相关蛋白（EGFR、AKT）、细胞周期相关蛋白CDK4表达,促进细胞凋亡蛋白BAX表达。结论 MeCP2在卵巢浆液性囊腺癌组织中低表达且与患者无病生存期相关,过表达MeCP2能够抑制卵巢浆液性囊腺癌SKOV3细胞的增殖。

Expression and significance of MeCP2 in ovarian serous cystadenocarcinoma

Objective To investigate the effect of Methyl-CpG-binding protein 2 （MeCP2） expression on the proliferation of ovarian serous cystadenocarcinoma SKOV3 cells. Methods RNA sequencing data and clinicopathological information of patients with ovarian serous cystadenocarcinoma were obtained from TCGA database. The correlation between the expression of MeCP2 in healthy people and patients with ovarian serous cystadenocarcinoma and the clinicopathological stage and survival time of ovarian serous cystadenocarcinoma was analyzed by bioinformatics method; MTT assay, cell cloning assay, cell cycle and apoptosis were used to analyze the effect of MeCP2 expression on the proliferation of SKOV3 cells. Gene set enrichment analysis （GSEA） was used to obtain the key signal pathway of MeCP2 expression regulation, and then Western blot was used to detect related proteins. Results The expression of MeCP2 decreased significantly in patients with ovarian serous cystadenocarcinoma; The expression of MeCP2 was related to the pathological stage of ovarian serous cystadenocarcinoma, but not to the histological grade; Survival analysis showed that the disease-free interval of patients with high expression of MeCP2 was significantly higher than that of patients with low expression, while the expression of MeCP2 had no effect on the overall survival,disease-specific survival and progression free interval of patients; Cell function experiment showed that overexpression of MeCP2 could inhibit cell proliferation activity, cell clone formation ability, block the transformation of G₁/S phase of cell cycle and induce apoptosis. The signal pathway analysis of MeCP2 expression regulation showed that MeCP2 could inhibit the expression of ERBB signal pathway related proteins （EGFR, AKT） and cell cycle related protein CDK4, and promote the expression of apoptosis protein Bax. Conclusion The low expression of MeCP2 in ovarian serous cystadenocarcinoma is related to the disease-free interval. Overexpression of MeCP2 can inhibit the proliferation of SKOV3 cells.