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

被引：184

作者：

Niknafs, Yashar S. ^{[1
,2
]}

Han, Sumin ^{[3
]}

Ma, Teng ^{[3
,4
]}

Speers, Corey ^{[3
,5
]}

Zhang, Chao ^{[3
]}

Wilder-Romans, Kari ^{[3
]}

Iyer, Matthew K. ^{[1
,7
]}

Pitchiaya, Sethuramasundaram ^{[1
]}

Malik, Rohit ^{[1
]}

Hosono, Yasuyuki ^{[1
]}

Prensner, John R. ^{[1
]}

Poliakov, Anton ^{[1
]}

Singhal, Udit ^{[1
,8
]}

Xiao, Lanbo ^{[1
]}

Kregel, Steven ^{[1
]}

Siebenaler, Ronald F.

Zhao, Shuang G. ^{[3
]}

Uhl, Michael ^{[9
,10
]}

Gawronski, Alexander ^{[11
]}

Hayes, Daniel F. ^{[6
,12
]}

Pierce, Lori J. ^{[3
,5
,6
]}

Cao, Xuhong ^{[1
,8
]}

Collins, Colin

Backofen, Rolf ^{[9
,10
]}

Sahinalp, Cenk S. ^{[11
,13
,14
]}

Rae, James M. ^{[5
,6
,12
]}

Chinnaiyan, Arul M. ^{[1
,2
,5
,6
,8
,15
,16
]}

Feng, Felix Y. ^{[1
,3
,5
,6
,17
,18
,19
]}

机构：

[1] Univ Michigan, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Cellular & Mol Biol, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA

[4] Beijing Inst Radiat Med, Dept Radiat Toxicol & Oncol, Beijing Key Lab Radiobiol BKLRB, Beijing 100850, Peoples R China

[5] Univ Michigan, Breast Oncol Program, Ann Arbor, MI 48109 USA

[6] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA

[7] Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA

[8] Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA

[9] Univ Freiburg, Dept Comp Sci, D-79110 Freiburg, Germany

[10] Univ Freiburg, Ctr Biol Signaling Studies BIOSS, D-79110 Freiburg, Germany

[11] Simon Fraser Univ, Sch Comp Sci, Burnaby, BC V5A 1S6, Canada

[12] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA

[13] Indiana Univ, Sch Informat & Comp, Bloomington, IN 47405 USA

[14] Vancouver Prostate Ctr, Vancouver, BC V6H 3Z6, Canada

[15] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

[16] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA

[17] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Radiat Oncol, San Francisco, CA 94115 USA

[18] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Urol, San Francisco, CA 94115 USA

[19] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Med, San Francisco, CA 94115 USA

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

美国国家卫生研究院;

关键词：

LONG NONCODING RNAS; GENE-EXPRESSION PATTERNS; ESTROGEN-RECEPTOR-ALPHA; HNRNP-L; MOLECULAR SUBTYPES; PROSTATE-CANCER; BINDING; SEQ; TRANSCRIPTOME; MICROARRAY;

D O I：

10.1038/ncomms12791

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

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