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

Whitney S. Henry, David G. Hendrickson, Francisco Beca, Benjamin Glass, Marianne Lindahl-Allen, Lizhi He, Zhe Ji, Kevin Struhl, Andrew H. Beck, John L. Rinn, Alex Toker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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. ShRNAmediated 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.

Original languageEnglish (US)
Pages (from-to)81981-81994
Number of pages14
JournalOncotarget
Volume7
Issue number50
DOIs
StatePublished - 2016

Keywords

  • Breast cancer
  • LINC00520
  • LncRNA
  • PI3K
  • Src

ASJC Scopus subject areas

  • Oncology

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