4-羟基他莫昔芬通过抑制DNMT1/DNMT3A表达逆转三阴性乳腺癌细胞间质表型  

4-Hydroxytamoxifen reverse mesenchymal type of triple negative breastcancer cells by inhibiting the expression of DNMT1/DNMT3A

作　　者：王一丁[1] 汪茜[2] WANG Yiding;WANG Qian(Department of Urology,Liaoning Cancer Hospital&Cancer Hospital Affiliated to China Medical University,Shenyang Liaoning 110042,China;Department of Gastroenterology,Liaoning Cancer Hospital&Cancer Hospital Affiliated to China Medical University,Shenyang Liaoning 110042,China)

机构地区：[1]辽宁省肿瘤医院,中国医科大学附属肿瘤医院泌尿外二科,辽宁沈阳110042 [2]辽宁省肿瘤医院,中国医科大学附属肿瘤医院消化内一科,辽宁沈阳110042

出　　处：《转化医学杂志》2020年第2期88-91,100,共5页Translational Medicine Journal

基　　金：国家自然科学基金青年项目(81902676);辽宁省博士科研启动基金指导计划项目(20170520005)。

摘　　要：目的探讨4-羟基他莫昔芬(4-hydroxytamoxifen,4-OHT)能否通过上调微小RNA-200c(microRNA-200c,miR-200c)表达抑制DNA甲基化转移酶(DNA methyltransferase,DNMT)1和DNMT3A,从而逆转三阴性乳腺癌(triple negative breast cancer,TNBC)细胞间质表型。方法采用Western Blot检测雌激素受体-α(estrogen receptor-α,ER-α)、孕激素受体(progesterone receptor,PR)及人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2),DNMT1,DNMT3A,Vimentin和Actin蛋白的表达。采用实时荧光定量PCR技术检测miR-200c的相对表达量。应用网络数据库及在线分析软件预测miR-200c启动子的CpG岛。结果不同表型乳腺癌细胞miR-200c表达差异显著;4-OHT上调TNBC细胞miR-200c表达;miR-200c启动子存在CpG岛;4-OHT能够上调miR-200c影响DNMT1/DNMT3A表达。结论TNBC细胞miR-200c表达降低,4-OHT能够上调TNBC细胞中miR-200c表达。4-OHT通过上调间质样TNBC细胞miR-200c表达,抑制DNMT1、DNMT3A表达,从而逆转间质样表达。Objective To investigate whether 4-hydroxytamoxifen(4-OHT)could upregulate the expression of microRNA-200c(miR-200c)by inhibiting the expression of DNA methyltransferase(DNMT)1/DNMT3A to reverse the mesenchymal type of triple negative breast cancer(TNBC).Methods Expression of estrogen receptor-α(ER-α),progesterone receptor(PR),human epidermal growth factor receptor-2(HER-2),DNMT1,DNMT3A,Vimentin and Actin proteins were analyzed by Western Blot.Relative levels of miR-200c were measured by real-time PCR.Data base online and online application was used to predict the existence of CpG island in the promoter of miR-200c.Results The expression of miR-200c was extremely different in three types of breast cancer cells.4-OHT upregulates the expression of miR-200c in TNBC cells.The promoter of miR-200c exist CpG island.4-OHT increases expression of miR-200c,which decrease the expression of DNMT1/DNMT3A in TNBC cells.Conclusion The expression of miR-200c in TNBC cells was low.4-OHT could upregulate the expression of miR-200c.4-OHT reversed mesenchymal type of TNBC cells by inhibiting the expression of DNMT1/DNMT3A.

关 键 词：三阴性乳腺癌 甲基化转移酶 4-羟基他莫昔芬 MicroRNA-200c 

分 类 号：R737.9[医药卫生—肿瘤]