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.

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