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. Hayes; Lori J. Pierce; Xuhong Cao; Colin Collins; Rolf Backofen; Cenk S. Sahinalp; James M. Rae; Arul M. Chinnaiyan; Felix Y. Feng

doi:10.1038/ncomms12791

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 journal › Article › peer-review

164 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 language	English
Article number	12791
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12791
Publication status	Published - Sept 26 2016
Externally published	Yes

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncomms12791

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Niknafs, Y. S., Han, S., Ma, T., Speers, C., Zhang, C., Wilder-Romans, K., Iyer, M. K., Pitchiaya, S., Malik, R., Hosono, Y., Prensner, J. R., Poliakov, A., Singhal, U., Xiao, L., Kregel, S., Siebenaler, R. F., Zhao, S. G., Uhl, M., Gawronski, A., ... Feng, F. Y. (2016). The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression. Nature communications, 7, [12791]. https://doi.org/10.1038/ncomms12791

Niknafs, YS, Han, S, Ma, T, Speers, C, Zhang, C, Wilder-Romans, K, Iyer, MK, Pitchiaya, S, Malik, R, Hosono, Y, Prensner, JR, Poliakov, A, Singhal, U, Xiao, L, Kregel, S, Siebenaler, RF, Zhao, SG, Uhl, M, Gawronski, A, Hayes, DF, Pierce, LJ, Cao, X, Collins, C, Backofen, R, Sahinalp, CS, Rae, JM, Chinnaiyan, AM & Feng, FY 2016, 'The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression', Nature communications, vol. 7, 12791. https://doi.org/10.1038/ncomms12791

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title = "The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression",

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.",

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

note = "Funding Information: This work was supported in part by US National Institutes of Health Prostate Specialized Program of Research Excellence grant P50CA186786, Early Detection Research Network grant UO1 CA111275, US National Institutes of Health grants R01 CA132874 and RO1 CA154365 (A.M.C.), and US Department of Defense grant PC100171 (A.M.C.). A.M.C. is supported by the Prostate Cancer Foundation and the Howard Hughes Medical Institute. A.M.C. is an American Cancer Society Research Professor and a Taubman Scholar of the University of Michigan. R.M. Publisher Copyright: {\textcopyright} The Author(s) 2016.",

year = "2016",

month = sep,

day = "26",

doi = "10.1038/ncomms12791",

language = "English",

volume = "7",

journal = "Nature Communications",

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T1 - The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression

AU - Niknafs, Yashar S.

AU - Han, Sumin

AU - Ma, Teng

AU - Speers, Corey

AU - Zhang, Chao

AU - Wilder-Romans, Kari

AU - Iyer, Matthew K.

AU - Pitchiaya, Sethuramasundaram

AU - Malik, Rohit

AU - Hosono, Yasuyuki

AU - Prensner, John R.

AU - Poliakov, Anton

AU - Singhal, Udit

AU - Xiao, Lanbo

AU - Kregel, Steven

AU - Siebenaler, Ronald F.

AU - Zhao, Shuang G.

AU - Uhl, Michael

AU - Gawronski, Alexander

AU - Hayes, Daniel F.

AU - Pierce, Lori J.

AU - Cao, Xuhong

AU - Collins, Colin

AU - Backofen, Rolf

AU - Sahinalp, Cenk S.

AU - Rae, James M.

AU - Chinnaiyan, Arul M.

AU - Feng, Felix Y.

N1 - Funding Information: This work was supported in part by US National Institutes of Health Prostate Specialized Program of Research Excellence grant P50CA186786, Early Detection Research Network grant UO1 CA111275, US National Institutes of Health grants R01 CA132874 and RO1 CA154365 (A.M.C.), and US Department of Defense grant PC100171 (A.M.C.). A.M.C. is supported by the Prostate Cancer Foundation and the Howard Hughes Medical Institute. A.M.C. is an American Cancer Society Research Professor and a Taubman Scholar of the University of Michigan. R.M. Publisher Copyright: © The Author(s) 2016.

PY - 2016/9/26

Y1 - 2016/9/26

N2 - 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.

AB - 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.

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DO - 10.1038/ncomms12791

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JO - Nature Communications

JF - Nature Communications

M1 - 12791

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

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