Long noncoding RNA MALAT1 suppresses breast cancer metastasis

doi:10.1038/s41588-018-0252-3

	Long noncoding RNA MALAT1 suppresses breast cancer metastasis
	Kim, Jongchan 1; Piao, Hai-Long 1,2; Kim, Beom-Jun 3; Yao, Fan 1; Han, Zhenbo 4; Wang, Yumeng 5; Xiao, Zhenna 1,6; Siverly, Ashley N.1; Lawhon, Sarah E.1; Ton, Baochau N.1
刊名	NATURE GENETICS
	2018-12-01
卷号	50 期号:12 页码:1705-+
ISSN号	1061-4036
DOI	10.1038/s41588-018-0252-3
通讯作者	Ma, Li(lma4@mdanderson.org)
英文摘要	MALAT1 has previously been described as a metastasis-promoting long noncoding RNA (lncRNA). We show here, however, that targeted inactivation of the Malat1 gene in a transgenic mouse model of breast cancer, without altering the expression of its adjacent genes, promotes lung metastasis, and that this phenotype can be reversed by genetic add-back of Malat1. Similarly, knockout of MALAT1 in human breast cancer cells induces their metastatic ability, which is reversed by re-expression of Malat1. Conversely, overexpression of Malat1 suppresses breast cancer metastasis in transgenic, xenograft, and syngeneic models. Mechanistically, the MALAT1 lncRNA binds and inactivates the prometastatic transcription factor TEAD, preventing TEAD from associating with its co-activator YAP and target gene promoters. Moreover, MALAT1 levels inversely correlate with breast cancer progression and metastatic ability. These findings demonstrate that MALAT1 is a metastasis-suppressing lncRNA rather than a metastasis promoter in breast cancer, calling for rectification of the model for this highly abundant and conserved lncRNA.
资助项目	US National Institutes of Health (NIH)[R01CA166051] ; US National Institutes of Health (NIH)[R01CA181029] ; Cancer Prevention and Research Institute of Texas (CPRIT)[RP150319] ; Stand Up To Cancer Innovative Research Grant[403235] ; NIH[R01CA164346] ; NIH[R01CA200703] ; NIH[R01CA175486] ; NIH[U24CA209851] ; NIH[R01CA181196] ; NIH[R01CA190370] ; CPRIT[RP140402] ; National Breast Cancer Foundation Inc. ; University of Texas MD Anderson-China Medical University and Hospital Sister Institution Fund ; CPRIT grant[RR140033]
WOS关键词	EPITHELIAL-MESENCHYMAL TRANSITION ; COLORECTAL-CANCER ; MAMMARY-TUMORS ; EMERGING ROLES ; YAP ; ACTIVATION ; EXPRESSION ; ONCOGENE ; BINDING ; GROWTH
WOS研究方向	Genetics & Heredity
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000451434400018
资助机构	US National Institutes of Health (NIH) ; US National Institutes of Health (NIH) ; Cancer Prevention and Research Institute of Texas (CPRIT) ; Cancer Prevention and Research Institute of Texas (CPRIT) ; Stand Up To Cancer Innovative Research Grant ; Stand Up To Cancer Innovative Research Grant ; NIH ; NIH ; CPRIT ; CPRIT ; National Breast Cancer Foundation Inc. ; National Breast Cancer Foundation Inc. ; University of Texas MD Anderson-China Medical University and Hospital Sister Institution Fund ; University of Texas MD Anderson-China Medical University and Hospital Sister Institution Fund ; CPRIT grant ; CPRIT grant ; US National Institutes of Health (NIH) ; US National Institutes of Health (NIH) ; Cancer Prevention and Research Institute of Texas (CPRIT) ; Cancer Prevention and Research Institute of Texas (CPRIT) ; Stand Up To Cancer Innovative Research Grant ; Stand Up To Cancer Innovative Research Grant ; NIH ; NIH ; CPRIT ; CPRIT ; National Breast Cancer Foundation Inc. ; National Breast Cancer Foundation Inc. ; University of Texas MD Anderson-China Medical University and Hospital Sister Institution Fund ; University of Texas MD Anderson-China Medical University and Hospital Sister Institution Fund ; CPRIT grant ; CPRIT grant ; US National Institutes of Health (NIH) ; US National Institutes of Health (NIH) ; Cancer Prevention and Research Institute of Texas (CPRIT) ; Cancer Prevention and Research Institute of Texas (CPRIT) ; Stand Up To Cancer Innovative Research Grant ; Stand Up To Cancer Innovative Research Grant ; NIH ; NIH ; CPRIT ; CPRIT ; National Breast Cancer Foundation Inc. ; National Breast Cancer Foundation Inc. ; University of Texas MD Anderson-China Medical University and Hospital Sister Institution Fund ; University of Texas MD Anderson-China Medical University and Hospital Sister Institution Fund ; CPRIT grant ; CPRIT grant ; US National Institutes of Health (NIH) ; US National Institutes of Health (NIH) ; Cancer Prevention and Research Institute of Texas (CPRIT) ; Cancer Prevention and Research Institute of Texas (CPRIT) ; Stand Up To Cancer Innovative Research Grant ; Stand Up To Cancer Innovative Research Grant ; NIH ; NIH ; CPRIT ; CPRIT ; National Breast Cancer Foundation Inc. ; National Breast Cancer Foundation Inc. ; University of Texas MD Anderson-China Medical University and Hospital Sister Institution Fund ; University of Texas MD Anderson-China Medical University and Hospital Sister Institution Fund ; CPRIT grant ; CPRIT grant
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/166508]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Ma, Li
作者单位	1.Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA 2.Chinese Acad Sci, Dalian Inst Chem Phys, Sci Res Ctr Translat Med, CAS Key Lab Separat Sci Analyt Chem, Dalian, Peoples R China 3.Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA 4.Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA 5.Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA 6.Univ Texas MD Anderson Canc Ctr, UTHlth Grad Sch Biomed Sci, Houston, TX 77030 USA 7.Hokkaido Univ, Fac Pharmaceut Sci, RNA Biol Lab, Sapporo, Hokkaido, Japan 8.China Med Univ, Grad Inst Biomed Sci, Taichung, Taiwan 9.China Med Univ, Ctr Mol Med, Taichung, Taiwan 10.Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA
推荐引用方式 GB/T 7714	Kim, Jongchan,Piao, Hai-Long,Kim, Beom-Jun,et al. Long noncoding RNA MALAT1 suppresses breast cancer metastasis[J]. NATURE GENETICS,2018,50(12):1705-+.
APA	Kim, Jongchan.,Piao, Hai-Long.,Kim, Beom-Jun.,Yao, Fan.,Han, Zhenbo.,...&Ma, Li.(2018).Long noncoding RNA MALAT1 suppresses breast cancer metastasis.NATURE GENETICS,50(12),1705-+.
MLA	Kim, Jongchan,et al."Long noncoding RNA MALAT1 suppresses breast cancer metastasis".NATURE GENETICS 50.12(2018):1705-+.