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表观遗传药物联合诱导口腔癌FMR1NB表达的研究
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作者 张煜萱 谢欢 +8 位作者 王燕靖 李枫 王国鉴 农蔚霞 刘畅 罗彬 谢小薰 沈宁 张庆梅 《安徽医科大学学报》 CAS 北大核心 2024年第5期761-766,共6页
目的研究DNA去甲基化药物联合组蛋白去乙酰化酶抑制剂对人口腔癌细胞脆性X智障基因1邻近蛋白(FMR1NB)表达及其启动子甲基化的影响,探寻改善FMR1NB表达异质性的方法和策略。方法DNA甲基化转移酶抑制剂地西他滨(DAC)联合组蛋白去乙酰化酶... 目的研究DNA去甲基化药物联合组蛋白去乙酰化酶抑制剂对人口腔癌细胞脆性X智障基因1邻近蛋白(FMR1NB)表达及其启动子甲基化的影响,探寻改善FMR1NB表达异质性的方法和策略。方法DNA甲基化转移酶抑制剂地西他滨(DAC)联合组蛋白去乙酰化酶抑制剂曲古抑菌素A(TSA)和丙戊酸(VPA)干预人舌鳞癌细胞株Cal27和SCC-9后,采用逆转录-聚合酶链式反应(RT-PCR)、实时定量RT-PCR(qRT-PCR)和蛋白印迹法(Western blot)检测干预前后FMR1NB的表达变化;焦磷酸测序法检测干预前后FMR1NB启动子甲基化的变化。结果与空白对照组相比,DAC及其与TSA和VPA联合组均能显著诱导Cal27和SCC-9中FMR1NB mRNA和蛋白的表达。与DAC单独组比较,Cal27中各联合用药组的FMR1NB mRNA表达水平均显著升高,但FMR1NB蛋白表达无明显变化;而SCC-9中除DAC与TSA联合组不能明显提升FMR1NB mRNA表达水平之外,其余各组均能引起FMR1NB mRNA和蛋白水平的显著升高。此外,两株细胞中FMR1NB mRNA和蛋白表达在三药联合组和各两药联合组之间差异均无统计学意义。进一步甲基化测定显示:除SCC-9的三药联合组之外,其余各给药组在两株细胞中FMR1NB启动子区的整体甲基化水平和所测各CpG位点的甲基化水平均有不同程度地降低。结论DAC及其TSA和VPA联合组普遍可介导FMR1NB启动子去甲基化而增强FMR1NB表达,其中两药联合组的增强表达作用更强。 展开更多
关键词 口腔癌 fmr1nb 表观遗传学药物 表达 甲基化
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FMR1NB Involved in Glioma Tumorigenesis Is a Promising Target for Prognosis and Therapy 被引量:2
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作者 Shui-qing BI Ya PENG +8 位作者 Zong-dang WEI Sheng-zhong YAO Bin LUO Ying-ying GE Xiao-xun XIE Wei-xia NONG Chang LIU Shao-wen XIAO Qing-mei ZHANG 《Current Medical Science》 SCIE CAS 2022年第4期803-816,共14页
Objective:Cancer/testis antigen FMR1NB is aberrantly expressed in various types of cancer,but not in normal tissues except for testis.This study aimed to investigate the expression and functional role of FMR1NB in gli... Objective:Cancer/testis antigen FMR1NB is aberrantly expressed in various types of cancer,but not in normal tissues except for testis.This study aimed to investigate the expression and functional role of FMR1NB in glioma.Methods:The expression of FMR1NB mRNA and protein was determined using RT-PCR and immunohistochemistry,respectively,in glioma specimens from 83 patients at follow-up.The effects of siRNA-mediated FMR1NB silencing on malignant biological behaviors were evaluated in glioma cell lines Al 72 and U251.Results:FMR1NB mRNA and protein expression was detected in 58.8%(77/131)and 46.34%(57/123)of glioma tissues,respectively.FMR1NB protein was positively correlated with World Health Organization grade and found to be an independent prognostic marker for poor outcome.Knockdown of FMR1NB induced apoptosis and suppressed proliferation,adhesion,migration,and invasion by modulating the expression of cyclin A,CDK2,caspase-3,E-cadherin,and N-cadherin in A172 and U251 cells.Conclusion:Our findings suggest that FMR1NB contributes to the tumorigenesis of glioma cells and may represent a potential prognostic biomarker and an attractive therapeutic target in glioma. 展开更多
关键词 cancer/testis antigen fmr1nb GLIOMA
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