LINC00520 is induced by Src, STAT3, and PI3K and plays a functional role in breast cancer.
LINC00520 is induced by Src, STAT3, and PI3K and plays a functional role in breast cancer.
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DOI：
10.18632/oncotarget.11962
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发表时间：
2016-12-13
期刊：
影响因子：
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通讯作者：
Toker A
中科院分区：
文献类型：
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作者：
Henry WS;Hendrickson DG;Beca F;Glass B;Lindahl-Allen M;He L;Ji Z;Struhl K;Beck AH;Rinn JL;Toker A
长链非编码rna （lncRNAs）与正常细胞稳态以及包括癌症在内的病理生理状况有关。在这里，我们对致癌的v-Src转化的乳腺上皮细胞进行了全球基因表达谱分析，并鉴定了一大批未表征的lncrna，这些lncrna可能参与乳腺癌的发展。具体来说，我们的分析揭示了一种新的lncRNA， LINC00520，在致癌v-Src的异位表达中上调，其方式依赖于转录因子STAT3。同样，LINC00520在由致癌PI3K转化的乳腺上皮细胞中也增加，在敲低突变体PIK3CA后其表达减少。另外的表达谱显示，LINC00520在人类乳腺癌的一个亚群中表达升高，在基底样分子亚型中优先富集。shrna介导的LINC00520缺失导致3D中细胞迁移减少和侵袭性结构丢失。RNA测序分析揭示了几个在LINC00520异位表达时差异表达的基因，其中一个重要的亚群也在v- src转化的MCF10A细胞中被诱导。总之，这些发现表明LINC00520是一个受致癌Src、PIK3CA和STAT3调控的lncRNA，可能与乳腺癌的分子病因有关。
Long non-coding RNAs (lncRNAs) have been implicated in normal cellular homeostasis as well as pathophysiological conditions, including cancer. Here we performed global gene expression profiling of mammary epithelial cells transformed by oncogenic v-Src, and identified a large subset of uncharacterized lncRNAs potentially involved in breast cancer development. Specifically, our analysis revealed a novel lncRNA, LINC00520 that is upregulated upon ectopic expression of oncogenic v-Src, in a manner that is dependent on the transcription factor STAT3. Similarly, LINC00520 is also increased in mammary epithelial cells transformed by oncogenic PI3K and its expression is decreased upon knockdown of mutant PIK3CA. Additional expression profiling highlight that LINC00520 is elevated in a subset of human breast carcinomas, with preferential enrichment in the basal-like molecular subtype. ShRNA-mediated depletion of LINC00520 results in decreased cell migration and loss of invasive structures in 3D. RNA sequencing analysis uncovers several genes that are differentially expressed upon ectopic expression of LINC00520, a significant subset of which are also induced in v-Src-transformed MCF10A cells. Together, these findings characterize LINC00520 as a lncRNA that is regulated by oncogenic Src, PIK3CA and STAT3, and which may contribute to the molecular etiology of breast cancer.