LincRNA-ROR induces epithelial-to-mesenchymal transition and contributes to breast cancer tumorigenesis and metastasis.
LincRNA-ROR induces epithelial-to-mesenchymal transition and contributes to breast cancer tumorigenesis and metastasis.
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LincRNA-ROR 诱导上皮间质转化并有助于乳腺癌肿瘤发生和转移
DOI：
10.1038/cddis.2014.249
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发表时间：
2014-06-12
影响因子：
9
通讯作者：
Lu J
中科院分区：
文献类型：
--
作者：
Hou P;Zhao Y;Li Z;Yao R;Ma M;Gao Y;Zhao L;Zhang Y;Huang B;Lu J
LncRNA在从胚胎发育到人类疾病（包括癌症进展）的各种生物过程中具有关键作用，尽管其详细的机制功能仍然是虚幻的。已显示lncRNA linc-ROR有助于维持诱导的多能干细胞和胚胎干细胞。在这项研究中，我们发现，linc-ROR在乳腺肿瘤样品中上调，并且在永生化的人乳腺上皮细胞中linc-ROR的异位过表达诱导了上皮向间充质转化（EMT）程序。此外，我们发现linc-ROR增强了乳腺癌细胞的迁移和侵袭，这伴随着干细胞特性的产生。因此，linc-ROR的沉默在体内抑制乳腺肿瘤生长和肺转移。从机制上讲，我们的数据显示linc-ROR与miRNP相关，并作为mi-205的竞争性内源RNA发挥作用。具体而言，linc-ROR阻止了mir-205靶基因的降解，包括EMT诱导剂ZEB 2。因此，我们的研究结果表明linc-ROR作为EMT的重要调节因子发挥作用，并可通过调节miRNA促进乳腺癌的进展和转移。本研究的发现可能暗示linc-ROR作为侵袭性和转移性乳腺癌的可能治疗靶点的相关性。
LncRNAs have critical roles in various biological processes ranging from embryonic development to human diseases, including cancer progression, although their detailed mechanistic functions remain illusive. The lncRNA linc-ROR has been shown to contribute to the maintenance of induced pluripotent stem cells and embryonic stem cells. In this study, we discovered that linc-ROR was upregulated in breast tumor samples, and ectopic overexpression of linc-ROR in immortalized human mammary epithelial cells induced an epithelial-to-mesenchymal transition (EMT) program. Moreover, we showed that linc-ROR enhanced breast cancer cell migration and invasion, which was accompanied by generation of stem cell properties. Contrarily, silencing of linc-ROR repressed breast tumor growth and lung metastasis in vivo. Mechanistically, our data revealed that linc-ROR was associated with miRNPs and functioned as a competing endogenous RNA to mi-205. Specifically, linc-ROR prevented the degradation of mir-205 target genes, including the EMT inducer ZEB2. Thus our results indicate that linc-ROR functions as an important regulator of EMT and can promote breast cancer progression and metastasis through regulation of miRNAs. Potentially, the findings of this study implicate the relevance of linc-ROR as a possible therapeutic target for aggressive and metastatic breast cancers.