DSCAM-AS1 regulates the G1 /S cell cycle transition and is an independent prognostic factor of poor survival in luminal breast cancer patients treated with endocrine therapy

Wei Sun; An-Qi Li; Ping Zhou; Yi-Zhou Jiang; Xi Jin; Yi-Rong Liu; Ya-Jie Guo; Wen-Tao Yang; Zhi-Ming Shao; Xiao-En Xu

doi:10.1002/cam4.1603

DSCAM-AS1 regulates the G₁ /S cell cycle transition and is an independent prognostic factor of poor survival in luminal breast cancer patients treated with endocrine therapy

Cancer Med. 2018 Dec;7(12):6137-6146. doi: 10.1002/cam4.1603. Epub 2018 Nov 14.

Authors

Wei Sun^{1

2

3}, An-Qi Li^{2

3

4}, Ping Zhou⁵, Yi-Zhou Jiang^{1

2

3}, Xi Jin^{1

2

3}, Yi-Rong Liu^{1

2

3}, Ya-Jie Guo^{1

2

3}, Wen-Tao Yang^{2

3

4}, Zhi-Ming Shao^{1

2

3

6}, Xiao-En Xu^{1

2

3}

Affiliations

¹ Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
² Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.
³ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
⁴ Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
⁵ Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang, China.
⁶ Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

Abstract

DSCAM-AS1 is one of the few intensively studied lncRNAs with high specific expression in luminal breast cancer. It is directly regulated by estrogen receptor α (ERα) and plays vital roles in tumor proliferation, invasion, and tamoxifen resistance. However, the detailed function of DSCAM-AS1 in tumor progression and its clinical significance remain unclear. We reveal that DSCAM-AS1 regulates cell proliferation and colony formation by inducing the G1/S transition. RNA-seq analysis demonstrated that DSCAM-AS1 participates in crucial biological processes, including DNA replication, the G1/S phase transition, sister chromatid cohesion, chromosome segregation, protein localization to the chromosome and DNA recombination. Most importantly, in the retrospectively registered clinical analysis, high expression of DSCAM-AS1 is a poor prognostic factor in patients with luminal breast cancer treated with endocrine therapy. In conclusion, DSCAM-AS1 is a promising clinical therapeutic target that may prolong survival of luminal breast cancer patients treated with endocrine therapy.

Keywords: DSCAM-AS1; endocrine therapy; long noncoding RNA; luminal breast cancer; prognostic factor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antineoplastic Agents, Hormonal / therapeutic use
Breast Neoplasms / drug therapy
Breast Neoplasms / genetics*
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Disease-Free Survival
Drug Resistance, Neoplasm
Female
Humans
Middle Aged
Prognosis
RNA, Long Noncoding*
Tamoxifen / therapeutic use

Substances

Antineoplastic Agents, Hormonal
RNA, Long Noncoding
long noncoding RNA DSCAM-AS1, human
Tamoxifen