Emerging role of long non-coding RNA SOX2OT in SOX2 regulation in breast cancer

PLoS One. 2014 Jul 9;9(7):e102140. doi: 10.1371/journal.pone.0102140. eCollection 2014.

Abstract

The transcription factor SOX2 is essential for maintaining pluripotency in a variety of stem cells. It has important functions during embryonic development, is involved in cancer stem cell maintenance, and is often deregulated in cancer. The mechanism of SOX2 regulation has yet to be clarified, but the SOX2 gene lies in an intron of a long multi-exon non-coding RNA called SOX2 overlapping transcript (SOX2OT). Here, we show that the expression of SOX2 and SOX2OT is concordant in breast cancer, differentially expressed in estrogen receptor positive and negative breast cancer samples and that both are up-regulated in suspension culture conditions that favor growth of stem cell phenotypes. Importantly, ectopic expression of SOX2OT led to an almost 20-fold increase in SOX2 expression, together with a reduced proliferation and increased breast cancer cell anchorage-independent growth. We propose that SOX2OT plays a key role in the induction and/or maintenance of SOX2 expression in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cell Differentiation
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mammary Neoplasms, Experimental
  • Mice
  • Neoplastic Stem Cells / metabolism
  • RNA, Long Noncoding / genetics*
  • SOXB1 Transcription Factors / genetics*
  • Up-Regulation

Substances

  • RNA, Long Noncoding
  • SOXB1 Transcription Factors

Grants and funding

Funding for this work was obtained from the New Zealand Breast Cancer Foundation, the Maurice and Phyllis Paykel trust, Auckland Medical Research Foundation, and the Robert McClelland Trust. This work is also supported by Auckland Cancer Society Research Centre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.