CCAT1 promotes triple-negative breast cancer progression by suppressing miR-218/ZFX signaling
CCAT1 promotes triple-negative breast cancer progression by suppressing miR-218/ZFX signaling
复制标题
CCAT1 通过抑制 miR-218/ZFX 信号传导促进三阴性乳腺癌进展
DOI：
10.18632/aging.102080
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发表时间：
2019-07-31
期刊：
影响因子：
5.2
通讯作者：
Yin, Jian
中科院分区：
文献类型：
--
作者：
Han, Chunyong;Li, Xuebiao;Yin, Jian
长链非编码RNA（lncRNA）调节癌症的发生和发展。在这里，我们研究了lncRNA CCAT 1在三阴性乳腺癌（TNBC）中的作用。CCAT 1在TNBC细胞中的表达高于正常乳腺上皮细胞。此外，TNBC患者肿瘤组织中的CCAT 1表达高于邻近的正常乳腺组织。沉默CCAT 1在体外抑制TNBC细胞增殖、迁移和侵袭，在体内抑制肿瘤生长和进展。生物信息学分析显示microRNA-218（miR-218）是CCAT 1的潜在靶点。沉默CCAT 1导致miR-218表达增加，并抑制TNBC细胞增殖、迁移和侵袭。沉默miR-218逆转了CCAT 1敲低对细胞增殖、迁移和侵袭的影响，表明CCAT 1通过下调miR-218表达促进TNBC进展。我们通过生物信息学分析确定锌指蛋白ZFX为miR-218的推定下游靶标。ZFX在TNBC中的表达高于正常乳腺细胞系，并且在TNBC肿瘤组织中的表达高于邻近的正常乳腺组织。ZFX的过表达逆转了miR-218对TNBC细胞增殖、迁移和侵袭的肿瘤抑制作用。我们的数据表明，CCAT 1通过靶向miR-218/ZFX轴促进TNBC进展。
Long non-coding RNAs (lncRNAs) regulate cancer development and progression. Here, we investigated the role of the lncRNA CCAT1 in triple-negative breast cancer (TNBC). CCAT1 expression was higher in TNBC cells than normal breast epithelial cells. Additionally, CCAT1 expression was higher in TNBC patient tumor tissue than adjacent normal breast tissue. Silencing CCAT1 inhibited TNBC cell proliferation, migration, and invasion in vitro, and tumor growth and progression in vivo. Bioinformatics analysis revealed that microRNA-218 (miR-218) is a potential target of CCAT1. Silencing CCAT1 resulted in an increase in miR-218 expression and inhibited TNBC cell proliferation, migration, and invasion. Silencing miR-218 reversed the effects of CCAT1 knockdown on cell proliferation, migration, and invasion, suggesting that CCAT1 promotes TNBC progression by downregulating miR-218 expression. We identified the zinc finger protein ZFX as a putative downstream target of miR-218 through bioinformatics analysis. ZFX expression was higher in TNBC than normal breast cell lines and higher in TNBC tumor tissue than adjacent normal breast tissue. Overexpression of ZFX reversed the tumor-suppressive effects of miR-218 on TNBC cell proliferation, migration, and invasion. Our data indicate that CCAT1 promotes TNBC progression by targeting the miR-218/ZFX axis.