LINC00520 is induced by Src, STAT3, and PI3K and plays a functional role in breast cancer

// Whitney S. Henry 1,* , David G. Hendrickson 2,3,* , Francisco Beca 1 , Benjamin Glass 1 , Marianne Lindahl-Allen 4 , Lizhi He 4 , Zhe Ji 4 , Kevin Struhl 4 , Andrew H. Beck 1 , John L. Rinn 2,3 and Alex Toker 1 1 Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 2 Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA 3 Broad Institute of MIT and Harvard, Cambridge, MA, USA 4 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA * These authors have contributed equally to this work Correspondence to: Alex Toker, email: // John L. Rinn, email: // Keywords : lncRNA, Src, PI3K, breast cancer, LINC00520 Received : March 29, 2016 Accepted : September 02, 2016 Published : September 10, 2016 Abstract 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.