Silencing DSCAM-AS1 suppresses the growth and invasion of ER-positive breast cancer cells by downregulating both DCTPP1 and QPRT
Silencing DSCAM-AS1 suppresses the growth and invasion of ER-positive breast cancer cells by downregulating both DCTPP1 and QPRT
复制标题
沉默 DSCAM-AS1 通过下调 DCTPP1 和 QPRT 抑制 ER 阳性乳腺癌细胞的生长和侵袭
DOI：
10.18632/aging.103538
复制
发表时间：
2020-07-31
期刊：
影响因子：
5.2
通讯作者：
Huang Yuanxi
中科院分区：
文献类型：
--
作者：
Zhang Yue;Jia Shusheng;Huang Yuanxi
乳腺癌（BC）仍然是对妇女健康的重大威胁；然而，BC的发生和发展机制尚不清楚。我们分析了来自基因表达Omnibus数据库和癌症基因组图谱数据集的数据，以确定BC和正常组织之间的差异表达基因。研究了敲低或过表达dCTP焦磷酸酶1 （DCTPP1）和喹啉酸磷酸核糖基转移酶（QPRT）在BC细胞中的作用。采用荧光素酶报告基因法、RNA免疫沉淀法、RNA下拉法、染色质免疫沉淀法和荧光原位杂交法检测唐氏综合征细胞粘附分子反义RNA 1 （DSCAM-AS1）对DCTPP1和QPRT表达的调控作用。与正常组织相比，DCTPP1和QPRT在BC中过表达。DCTPP1和QPRT的过表达与BC进展不良相关，促进MCF7和T47D细胞的生长、迁移和侵袭，但抑制凋亡。DSCAM-AS1通过竞争性结合miRNA-150-5p和miRNA-2467-3p增加QPRT表达。DSCAM-AS1通过影响H3K27乙酰化促进DCTPP1基因转录，通过结合3 '非翻译区增强DCTPP1 mRNA稳定性，共同导致DCTPP1过表达。总体而言，DSCAM-AS1敲低可降低DCTPP1和QPRT的表达，抑制雌激素受体阳性BC的生长、迁移和侵袭。
Breast cancer (BC) remains a significant threat to the health of women; however, the mechanism underlying the initiation and progression of BC is poorly understood. We analyzed data from the Gene Expression Omnibus database and The Cancer Genome Atlas datasets to identify differentially expressed genes between BC and normal tissues. The roles of dCTP pyrophosphatase 1 (DCTPP1) and quinolinate phosphoribosyltransferase (QPRT) in BC cells were investigated after knocking down or overexpressing the genes. The regulatory effects of Down syndrome cell adhesion molecule antisense RNA 1 (DSCAM-AS1) on DCTPP1 and QPRT expression were determined using luciferase reporter, RNA immunoprecipitation, RNA pull-down, chromatin immunoprecipitation, and fluorescence in situ hybridization assays. DCTPP1 and QPRT were overexpressed in BC compared to normal tissues. Overexpression of DCTPP1 and QPRT was associated with poor BC progression and promoted growth, migration, and invasion of MCF7 and T47D cells but inhibited apoptosis. DSCAM-AS1 increased QPRT expression via competitively binding miRNA-150-5p and miRNA-2467-3p. DSCAM-AS1 promoted DCTPP1 gene transcription by affecting H3K27 acetylation and enhanced DCTPP1 mRNA stability by binding to the 3′ untranslated region, which collectively resulted in DCTPP1 overexpression. Overall, DSCAM-AS1 knockdown decreased both DCTPP1 and QPRT expression, inhibiting the growth, migration, and invasion of estrogen receptor-positive BC.