The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression

Yashar S. Niknafs, Sumin Han, Teng Ma, Corey Speers, Chao Zhang, Kari Wilder-Romans, Matthew K. Iyer, Sethuramasundaram Pitchiaya, Rohit Malik, Yasuyuki Hosono, John R. Prensner, Anton Poliakov, Udit Singhal, Lanbo Xiao, Steven Kregel, Ronald F. Siebenaler, Shuang G. Zhao, Michael Uhl, Alexander Gawronski, Daniel F. HayesLori J. Pierce, Xuhong Cao, Colin Collins, Rolf Backofen, Cenk S. Sahinalp, James M. Rae, Arul M. Chinnaiyan, Felix Y. Feng

Research output: Contribution to journalArticlepeer-review

157 Citations (Scopus)

Abstract

Molecular classification of cancers into subtypes has resulted in an advance in our understanding of tumour biology and treatment response across multiple tumour types. However, to date, cancer profiling has largely focused on protein-coding genes, which comprise <1% of the genome. Here we leverage a compendium of 58,648 long noncoding RNAs (lncRNAs) to subtype 947 breast cancer samples. We show that lncRNA-based profiling categorizes breast tumours by their known molecular subtypes in breast cancer. We identify a cohort of breast cancer-associated and oestrogen-regulated lncRNAs, and investigate the role of the top prioritized oestrogen receptor (ER)-regulated lncRNA, DSCAM-AS1. We demonstrate that DSCAM-AS1 mediates tumour progression and tamoxifen resistance and identify hnRNPL as an interacting protein involved in the mechanism of DSCAM-AS1 action. By highlighting the role of DSCAM-AS1 in breast cancer biology and treatment resistance, this study provides insight into the potential clinical implications of lncRNAs in breast cancer.

Original languageEnglish
Article number12791
JournalNature communications
Volume7
DOIs
Publication statusPublished - Sep 26 2016
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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