Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Department of Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Nat Commun. 2016 Sep 26;7:12791. doi: 10.1038/ncomms12791.
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.
癌症的分子分类已经使我们对多种肿瘤类型的肿瘤生物学和治疗反应有了更深入的了解。然而,到目前为止,癌症分析主要集中在蛋白质编码基因上,这些基因仅占基因组的<1%。在这里,我们利用 58648 个长非编码 RNA(lncRNA)的汇编来对 947 个乳腺癌样本进行亚型分类。我们表明,基于 lncRNA 的分析可以根据乳腺癌的已知分子亚型对乳腺癌进行分类。我们鉴定了一组与乳腺癌相关和雌激素调节的 lncRNA,并研究了优先级最高的雌激素受体(ER)调节的 lncRNA,DSCAM-AS1 的作用。我们证明 DSCAM-AS1 介导肿瘤进展和他莫昔芬耐药,并确定 hnRNPL 是参与 DSCAM-AS1 作用机制的相互作用蛋白。通过强调 DSCAM-AS1 在乳腺癌生物学和治疗耐药性中的作用,本研究为 lncRNA 在乳腺癌中的潜在临床意义提供了新的见解。