Long noncoding RNA MALAT1 suppresses breast cancer metastasis.
Long noncoding RNA MALAT1 suppresses breast cancer metastasis.
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DOI：
10.1038/s41588-018-0252-3
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发表时间：
2018-12
期刊：
影响因子：
30.8
通讯作者：
Ma L
中科院分区：
文献类型：
--
作者：
Kim J;Piao HL;Kim BJ;Yao F;Han Z;Wang Y;Xiao Z;Siverly AN;Lawhon SE;Ton BN;Lee H;Zhou Z;Gan B;Nakagawa S;Ellis MJ;Liang H;Hung MC;You MJ;Sun Y;Ma L
MALAT1以前被描述为促进转移的长非编码RNA（lncRNA）。出乎意料的是，我们发现，在乳腺癌转基因小鼠模型中，Malat 1基因的靶向失活而不改变其相邻基因的表达促进了肺转移，重要的是，这种表型被Malat 1的遗传回加逆转。类似地，人类乳腺癌细胞中MALAT1的敲除诱导了它们的转移能力，这被Malat1重新表达逆转。相反，在转基因、异种移植和同基因模型中，Malat 1的过表达抑制了乳腺癌转移。在机制上，MALAT1结合并灭活促转移转录因子TEAD，阻断TEAD与其共激活因子雅普和靶基因启动子的结合。此外，MALAT1水平与乳腺癌进展和转移能力呈负相关。这些发现表明，MALAT1是一种转移抑制lncRNA，而不是乳腺癌中的转移启动子，要求纠正高度丰富和保守的lncRNA模型。
MALAT1 has previously been described as a metastasis-promoting long non-coding RNA (lncRNA). Unexpectedly, we found that targeted inactivation of the Malat1 gene without altering the expression of its adjacent genes in a transgenic mouse model of breast cancer promoted lung metastasis, and importantly, this phenotype was reversed by genetic add-back of Malat1. Similarly, knockout of MALAT1 in human breast cancer cells induced their metastatic ability, which was reversed by Malat1 re-expression. Conversely, overexpression of Malat1 suppressed breast cancer metastasis in transgenic, xenograft, and syngeneic models. Mechanistically, MALAT1 binds and inactivates the pro-metastatic transcription factor TEAD, blocking 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 a highly abundant and conserved lncRNA.
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影响因子：
11.2
作者：
Kim J;Siverly AN;Chen D;Wang M;Yuan Y;Wang Y;Lee H;Zhang J;Muller WJ;Liang H;Gan B;Yang X;Sun Y;You MJ;Ma L
通讯作者：
Ma L
影响因子：
8.8
作者：
Bhattacharya R;Fan F;Wang R;Ye X;Xia L;Boulbes D;Ellis LM
通讯作者：
Ellis LM
影响因子：
4.4
作者：
Jiang G;Zhang S;Yazdanparast A;Li M;Pawar AV;Liu Y;Inavolu SM;Cheng L
通讯作者：
Cheng L
影响因子：
7.7
作者：
Bassett AR;Akhtar A;Barlow DP;Bird AP;Brockdorff N;Duboule D;Ephrussi A;Ferguson-Smith AC;Gingeras TR;Haerty W;Higgs DR;Miska EA;Ponting CP
通讯作者：
Ponting CP
影响因子：
5.3
作者：
GUY, CT;CARDIFF, RD;MULLER, WJ
通讯作者：
MULLER, WJ