lncRNA-TTC39A-AS1通过调控雌激素受体靶基因促进雌激素受体阳性乳腺癌细胞生长增殖  

lncRNA-TTC39A-AS1 promotes the growth and proliferation of estrogen receptor positive breast cancer cells by regulating estrogen receptor target genes

作　　者：张君娜 Zhang Junna(Department of Pathology,the First Affiliated Hospital of Henan University,Henan Kaifeng 475001,China)

机构地区：[1]河南大学第一附属医院病理科,河南开封475001

出　　处：《现代肿瘤医学》2020年第9期1426-1433,共8页Journal of Modern Oncology

基　　金：国家自然科学基金资助项目(编号:81501567);河南省高等学校重点科研项目(编号:19A320001)。

摘　　要：目的:系统筛选受雌激素显著调控且极具临床意义的lncRNA,并探究这些lncRNA如何参与雌激素受体阳性乳腺癌的发生发展。方法:通过全转录组高通量测序(RNA-seq)结合生物信息分析找到受雌激素显著诱导的lncRNA;结合GEPIA数据库找到受雌激素显著调控且在乳腺癌临床样品中特异高表达的lncRNA(TTC39A-AS1);利用PhyloCSF分析方法分析TTC39A-AS1是否具有编码能力;通过MTS、克隆形成实验及流式细胞术检测TTC39A-AS1对乳腺癌细胞的生长增殖及细胞周期的影响;利用LncAtlas数据库及核质分离结合qRT-PCR检测TTC39A-AS1的细胞内定位情况;在雌激素存在与否情况下,利用qRT-PCR检测敲低TTC39A-AS1后对雌激素靶基因表达的影响情况。结果:TTC39A-AS1被雌激素显著上调且在仅乳腺癌中特异性高表达;TTC39A-AS1不具有编码能力,是典型的长链非编码RNA;TTC39A-AS1促进乳腺癌细胞的生长增殖和克隆形成,当敲低TTC39A-AS1时会使乳腺癌细胞周期显著阻滞在G1期;TTC39A-AS1在细胞核和细胞质中都有分布;TTC39A-AS1被敲降后显著下调了雌激素靶基因的表达。结论:lncRNA-TTC39A-AS1受雌激素显著诱导且通过增强雌激素靶基因的表达促进雌激素受体阳性乳腺癌细胞生长增殖,因其仅在乳腺癌中特异性高表达属性,故可作为非常有前景的潜在的乳腺癌临床治疗靶点。Objective:To systematically screen lncRNAs that are significantly regulated by estrogen and to study the function and molecular mechanism of these lncRNAs in estrogen receptor positive breast cancer.Methods:lncRNA significantly induced by estrogen was identified by whole transcriptome sequencing combined with bioinformatics analysis,and combined with the GEPIA database,lncRNA(TTC39A-AS1),which is significantly regulated by estrogen and specifically expressed in breast cancer clinical samples,was found.PhyloCSF analysis was used to analyze whether TTC39A-AS1 had coding potential.MTS,clone formation assay and flow cytometry were used to detect the effect of TTC39A-AS1 on the growth,proliferation and cell cycle of breast cancer cells.The intracellular localization of TTC39A-AS1 was detected by LncAtlas database and nuclear isolation combined with qRT-PCR.The effect of knockdown of TTC39A-AS1 on the expression of estrogen target gene was detected by qRT-PCR in the presence or absence of estrogen.Results:TTC39A-AS1 was significantly up-regulated by estrogen and specifically expressed in breast cancer alone.TTC39A-AS1 had no coding potential and was a typical long non-coding RNA.TTC39A-AS1 promoted growth,proliferation and colony formation of breast cancer cells.When knocking down TTC39A-AS1,the cell cycle of breast cancer cell was significantly arrested in G1 phase.TTC39A-AS1 was distributed in both nucleus and cytoplasm.TTC39A-AS1 knocked down reduced the expression of estrogen target genes significantly.Conclusion:lncRNA-TTC39A-AS1 is significantly induced by estrogen and promotes the growth and proliferation of estrogen receptor positive breast cancer cells by enhancing the expression of estrogen target genes.Because it is only highly specific in breast cancer,it can be a promising potential clinical target for breast cancer treatment.

关 键 词：雌激素受体阳性乳腺癌 TTC39A-AS1 高通量测序 

分 类 号：R737.9[医药卫生—肿瘤]