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CCAT1通过抑制miR-218/ZFX信号通路促进三阴性乳腺癌进展。

CCAT1 promotes triple-negative breast cancer progression by suppressing miR-218/ZFX signaling.

作者信息

Han Chunyong, Li Xuebiao, Fan Qian, Liu Guangshu, Yin Jian

机构信息

Department of Breast Reconstruction, The Sino-Russian Joint Research Center for Oncoplastic Breast Surgery, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Treatment of Tianjin; Tianjin Clinical Research Center for Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin 300060, China.

Department of Cardiovascular Surgery, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China.

出版信息

Aging (Albany NY). 2019 Jul 16;11(14):4858-4875. doi: 10.18632/aging.102080.

Abstract

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 , and tumor growth and progression . 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.

摘要

长链非编码RNA(lncRNAs)调控癌症的发生和发展。在此,我们研究了lncRNA CCAT1在三阴性乳腺癌(TNBC)中的作用。CCAT1在TNBC细胞中的表达高于正常乳腺上皮细胞。此外,CCAT1在TNBC患者肿瘤组织中的表达高于相邻的正常乳腺组织。沉默CCAT1可抑制TNBC细胞的增殖、迁移和侵袭,以及肿瘤的生长和进展。生物信息学分析显示,微小RNA-218(miR-218)是CCAT1的一个潜在靶点。沉默CCAT1导致miR-218表达增加,并抑制TNBC细胞的增殖、迁移和侵袭。沉默miR-218可逆转CCAT1敲低对细胞增殖、迁移和侵袭的影响,表明CCAT1通过下调miR-218表达促进TNBC进展。通过生物信息学分析,我们确定锌指蛋白ZFX是miR-218的一个假定下游靶点。ZFX在TNBC中的表达高于正常乳腺细胞系,在TNBC肿瘤组织中的表达高于相邻的正常乳腺组织。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,CCAT1通过靶向miR-218/ZFX轴促进TNBC进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ce1/6682511/e481f0ebd674/aging-11-102080-g001.jpg

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