Alu RNA accumulation induces epithelial-to-mesenchymal transition by modulating miR-566 and is associated with cancer progression.
Alu RNA accumulation induces epithelial-to-mesenchymal transition by modulating miR-566 and is associated with cancer progression.
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DOI：
10.1038/onc.2017.369
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发表时间：
2018-02-01
期刊：
影响因子：
8
通讯作者：
Tarallo V
中科院分区：
文献类型：
--
作者：
Di Ruocco F;Basso V;Rivoire M;Mehlen P;Ambati J;De Falco S;Tarallo V
Alu序列是人类基因组中最丰富的短间隔重复序列。在这里，我们表明，在结直肠癌（CRC）进展的细胞培养模型中，我们观察到与DICER 1水平降低相关的Alu RNA积累。Alu RNA通过充当miR-566的分子海绵诱导上皮向间充质转化（EMT）。此外，由于DICER 1缺陷，Alu RNA在结直肠癌、卵巢癌、肾癌和乳腺癌细胞系中积累。有趣的是，Alu RNA敲低阻止了DICER 1耗竭诱导的EMT，尽管整体microRNA（miRNA）下调。Alu RNA表达也由转化生长因子-β1诱导，转化生长因子-β1是EMT的主要驱动因素。为了证实这些数据，我们发现非编码Alu RNA与人类CRC患者的肿瘤进展显著相关。总之，这些发现揭示了Alu RNA在癌症进展中的意想不到的DICER 1依赖性、miRNA非依赖性作用，这可能将移动的元件转录物带入癌症治疗和预后领域。
Alu sequences are the most abundant short interspersed repeated elements in the human genome. Here we show that in a cell culture model of colorectal cancer (CRC) progression, we observe accumulation of Alu RNA that is associated with reduced DICER1 levels. Alu RNA induces epithelial-to-mesenchymal transition (EMT) by acting as a molecular sponge of miR-566. Moreover, Alu RNA accumulates as consequence of DICER1 deficit in colorectal, ovarian, renal and breast cancer cell lines. Interestingly, Alu RNA knockdown prevents DICER1 depletion-induced EMT despite global microRNA (miRNA) downregulation. Alu RNA expression is also induced by transforming growth factor-β1, a major driver of EMT. Corroborating this data, we found that non-coding Alu RNA significantly correlates with tumor progression in human CRC patients. Together, these findings reveal an unexpected DICER1-dependent, miRNA-independent role of Alu RNA in cancer progression that could bring mobile element transcripts in the fields of cancer therapeutic and prognosis.
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DOI：
10.1126/science.aac7442
发表时间：
2015-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hung T;Pratt GA;Sundararaman B;Townsend MJ;Chaivorapol C;Bhangale T;Graham RR;Ortmann W;Criswell LA;Yeo GW;Behrens TW
通讯作者：
Behrens TW
影响因子：
3.7
作者：
Drusco A;Nuovo GJ;Zanesi N;Di Leva G;Pichiorri F;Volinia S;Fernandez C;Antenucci A;Costinean S;Bottoni A;Rosito IA;Liu CG;Burch A;Acunzo M;Pekarsky Y;Alder H;Ciardi A;Croce CM
通讯作者：
Croce CM
影响因子：
56.9
作者：
Kim, Jongpil;Inoue, Keiichi;Abeliovich, Asa
通讯作者：
Abeliovich, Asa
影响因子：
6.4
作者：
Daskalos, Alexandros;Nikolaidis, Georgios;Liloglou, Triantafillos
通讯作者：
Liloglou, Triantafillos
DOI：
10.1007/978-1-60327-367-1_8
发表时间：
2010-01-01
期刊：
GENETIC VARIATION: METHODS AND PROTOCOLS
影响因子：
--
作者：
Cordaux, Richard;Sen, Shurjo K.;Batzer, Mark A.
通讯作者：
Batzer, Mark A.