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Alu RNA 积累通过调节 miR-566 诱导上皮-间充质转化，并与癌症进展相关。

Alu RNA accumulation induces epithelial-to-mesenchymal transition by modulating miR-566 and is associated with cancer progression.

机构信息

Angiogenesis Lab, Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso'-CNR, Naples, Italy.

Apoptosis, Cancer and Development Laboratory, Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, Lyon, France.

出版信息

Oncogene. 2018 Feb 1;37(5):627-637. doi: 10.1038/onc.2017.369. Epub 2017 Oct 9.

DOI:10.1038/onc.2017.369
PMID:28991230
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5799714/
Abstract

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.

摘要

Alu 序列是人类基因组中最丰富的短散在重复元件。在这里，我们在结直肠癌细胞（CRC）进展的细胞培养模型中观察到 Alu RNA 的积累，这与 DICER1 水平降低有关。Alu RNA 通过充当 miR-566 的分子海绵来诱导上皮-间充质转化（EMT）。此外，Alu RNA 在结直肠、卵巢、肾和乳腺癌细胞系中由于 DICER1 缺陷而积累。有趣的是，尽管全局 miRNA（miRNA）下调，Alu RNA 敲低仍可阻止 DICER1 耗竭诱导的 EMT。Alu RNA 的表达也受到转化生长因子-β1 的诱导，这是 EMT 的主要驱动因素。证实这一数据，我们发现非编码 Alu RNA 与人 CRC 患者的肿瘤进展显著相关。总之，这些发现揭示了 Alu RNA 在癌症进展中出乎意料的 DICER1 依赖性、miRNA 独立性作用，这可能使移动元件转录本进入癌症治疗和预后领域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c422/5799714/13b1e2f51b13/onc2017369f6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c422/5799714/13b1e2f51b13/onc2017369f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c422/5799714/31b31da6752b/onc2017369f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c422/5799714/0ab5de01b3f8/onc2017369f2.jpg
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