miR-221/222 activate the Wnt/beta-catenin signaling to promote triple-negative breast cancer

doi:10.1093/jmcb/mjy041

	miR-221/222 activate the Wnt/beta-catenin signaling to promote triple-negative breast cancer
	Liu, Sanhong1 ; Wang, Zifeng1 ; Liu, Zukai1,2 ; Shi, Shuo1 ; Zhang, Zhaoran1 ; Zhang, Jiawei1 ; Lin, Haifan1,2,3,4
	2018-08
发表期刊	JOURNAL OF MOLECULAR CELL BIOLOGY (IF:5.3[JCR-2023],6.1[5-Year])
ISSN	1674-2788
卷号	10 期号:4 页码:302-315
发表状态	已发表
DOI	10.1093/jmcb/mjy041
摘要	Triple-negative breast cancer (TNBC), characterized by the lack of expression of the estrogen receptor, the progesterone receptor, and the human epidermal growth factor receptor 2, is an aggressive form of cancer that conveys unpredictable and poor prognosis due to limited treatment options and lack of effective targeted therapies. Wnt/beta-catenin signaling is hyperactivated in TNBC, which promotes the progression of TNBC. However, the molecular mechanism of Wnt/beta-catenin activation in TNBC remains unknown. Here, we report the drastic overexpression of miR-221/222 in all of four TNBC cell lines and TNBC primary tumor samples from patients. Furthermore, we demonstrate by both ex vivo and xenograft experiments that inhibiting miR-221/222 expression in a TNBC cell line (MDA-MB-231) suppresses its proliferation, viability, epithelial-to-mesenchymal transition, and migration; whereas expressing miR-221/222 in a non-TNBC line (MCF7) promotes all of the above cancer properties. miR-221/222 achieve so by directly repressing multiple negative regulators of the Wnt/beta-catenin signaling pathway, including WIF1, SFRP2, DKK2, and AXIN2, to activate the pathway. Notably, the level of miR-221/222 expression is inversely correlated whereas that of WIF1, DKK2, SFRP2, and AXIN2 expression is positively correlated with the patient survival. Last, we show that anti-miR-221/222 significantly increases apoptotic cells with tamoxifen/Wnt3a treatment but not with cyclophosphamide/Wnt3a treatment. These results demonstrate that miR-221/222 activate the Wnt/beta-catenin signaling to promote the aggressiveness and TNBC properties of breast cancers, and thus reveal a new prospect for TNBC treatment.
关键词	miR-221/222 Wnt/beta-catenin triple-negative breast cancer
收录类别	SCI ; SCIE ; CSCD
语种	英语
资助项目	National Natural Science Foundation of China[81772798]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000450433500004
CSCD记录号	CSCD:6347809
出版者	OXFORD UNIV PRESS
WOS关键词	ESTROGEN-RECEPTOR-ALPHA ; TAMOXIFEN RESISTANCE ; FEEDBACK LOOP ; UP-REGULATION ; WNT ; PATHWAY ; CELLS ; TUMORIGENESIS ; MICRORNAS ; TARGETS
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/28678
专题	生命科学与技术学院免疫化学研究所_特聘教授组_干细胞生物学实验室生命科学与技术学院_硕士生
通讯作者	Liu, Sanhong; Lin, Haifan
作者单位	1.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 3.Yale Univ, Sch Med, Yale Stem Cell Ctr, New Haven, CT 06510 USA 4.Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA
第一作者单位	免疫化学研究所
通讯作者单位	免疫化学研究所; 生命科学与技术学院
第一作者的第一单位	免疫化学研究所
推荐引用方式 GB/T 7714	Liu, Sanhong,Wang, Zifeng,Liu, Zukai,et al. miR-221/222 activate the Wnt/beta-catenin signaling to promote triple-negative breast cancer[J]. JOURNAL OF MOLECULAR CELL BIOLOGY,2018,10(4):302-315.
APA	Liu, Sanhong.,Wang, Zifeng.,Liu, Zukai.,Shi, Shuo.,Zhang, Zhaoran.,...&Lin, Haifan.(2018).miR-221/222 activate the Wnt/beta-catenin signaling to promote triple-negative breast cancer.JOURNAL OF MOLECULAR CELL BIOLOGY,10(4),302-315.
MLA	Liu, Sanhong,et al."miR-221/222 activate the Wnt/beta-catenin signaling to promote triple-negative breast cancer".JOURNAL OF MOLECULAR CELL BIOLOGY 10.4(2018):302-315.