HOTAIR rs7958904多态性对乳腺癌细胞生长的影响  

Effect of HOTAIR rs7958904 Polymorphism on the Growth of Breast Cancer Cells

作　　者：周蓉蓉[1] 肖坚[2] 李群[3] 龚建平[3] 向春红 孙维华[4] ZHOU Rongrong;XIAO Jian;LI Qun;GONG Jianping;XIANG Chunhong;SUN Weihua(Department of Oncology Xiangya Hospital, Central South University, Changsha, Hunan, 410008,China;Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, 410008,China;Department of Pharmacy the Second People’s Hospital of Huaihua, Huaihua, Hunan, 418000,China;Department of Breast, the Second People’s Hospital of Huaihua, Huaihua, Hunan, 418000,China)

机构地区：[1]中南大学湘雅医院肿瘤科,湖南长沙410008 [2]中南大学湘雅医院药学部,湖南长沙410008 [3]怀化市第二人民医院药剂科,湖南怀化418000 [4]怀化市第二人民医院乳腺科,湖南怀化418000

出　　处：《肿瘤药学》2017年第6期648-653,共6页Anti-Tumor Pharmacy

基　　金：北京医学奖励基金会基金资助项目(YJHYXKYJJ-601);湖南省卫生计生委科研计划课题资助项目(20160352)

摘　　要：目的探讨长链非编码RNA HOTAIR多态位点rs7958904对乳腺癌细胞生长的影响。方法分别将HOTAIR rs7958904野生型和突变型克隆进过表达载体,转染乳腺癌细胞;采用荧光定量PCR检测HOTAIR的表达,BrdU检测细胞增殖,流式细胞术检测细胞凋亡,transwell法检测细胞侵袭,Western blot检测MMP-2、MMP-9和Caspase-3的表达。结果突变型HOTAIR上调HOTAIR表达的效果明显低于野生型HOTAIR;野生型HOTAIR可显著促进乳腺癌细胞的增殖、抑制细胞凋亡,同时促进细胞侵袭;突变型HOTAIR具有类似作用,但效果明显低于野生型HOTAIR;野生型HOTAIR可显著促进MMP-2和MMP-9的表达,同时抑制活化Caspase-3的表达;突变型HOTAIR亦具有类似作用,但效果明显低于野生型HOTAIR。结论 HOTAIR rs7958904的突变型能下调HOTAIR的功能,从而影响乳腺癌细胞的生长。Objective To investigate the effects of lncRNA HOTAIR SNP rs7958904polymorphism on the growth of breast cancer(BC)cells.Methods The wild-type and mutant HOTAIR rs7958904gene were both cloned into the vector,respectively before being used to cotransfect the BC cells.Sequentially,in both wild-type and mutant transfected cell groups,HOTAIR expression was detected by fluorescent quantitative PCR,while cell proliferation and apoptosis were assessed by BrdU and flow cytometry,cell invasion was assessed by transwell migration assay,the expressions of MMP-2,MMP-9and Caspase-3were assessed by Western blot.Results The expression of HOTAIR was significantly lower in the mutant HOTAIR group than in the wild-type HOTAIR group.The wild-type HOTAIR was shown to significantly facilitate the proliferation and inhibit the apoptosis of BC cells;whereas mutant HOTAIR also exhibited the similar activity but such effect was significantly less dominant.At the same time,the wild-type HOTAIR was also associated with significant increment of MMP-2and MMP-9expressions,as well as significant inhibition of activated Caspase-3expression;although the mutant HOTIR also exhibited the same behaviors,but its effect was obviously insignificant when compared with the wild type.Conclusions The mutant HOTAIR rs7958904is able to regulate the expression of HOTAIR negatively,and thus affects the growth of BC cells.

关 键 词：长链非编码RNA HOTAIR 乳腺癌 单核苷酸多态性 

分 类 号：R737.9[医药卫生—肿瘤]