Links between the oncoprotein YB-1 and small non-coding RNAs in breast cancer

PLoS One. 2013 Nov 18;8(11):e80171. doi: 10.1371/journal.pone.0080171. eCollection 2013.

Abstract

Background: The nucleic acid-binding protein YB-1, a member of the cold-shock domain protein family, has been implicated in the progression of breast cancer and is associated with poor patient survival. YB-1 has sequence similarity to LIN28, another cold-shock protein family member, which has a role in the regulation of small noncoding RNAs (sncRNAs) including microRNAs (miRNAs). Therefore, to investigate whether there is an association between YB-1 and sncRNAs in breast cancer, we investigated whether sncRNAs were bound by YB-1 in two breast cancer cell lines (luminal A-like and basal cell-like), and whether the abundance of sncRNAs and mRNAs changed in response to experimental reduction of YB-1 expression.

Results: RNA-immunoprecipitation with an anti-YB-1 antibody showed that several sncRNAs are bound by YB-1. Some of these were bound by YB-1 in both breast cancer cell lines; others were cell-line specific. The small RNAs bound by YB-1 were derived from various sncRNA families including miRNAs such as let-7 and miR-320, transfer RNAs, ribosomal RNAs and small nucleolar RNAs (snoRNA). Reducing YB-1 expression altered the abundance of a number of transcripts encoding miRNA biogenesis and processing proteins but did not alter the abundance of mature or precursor miRNAs.

Conclusions: YB-1 binds to specific miRNAs, snoRNAs and tRNA-derived fragments and appears to regulate the expression of miRNA biogenesis and processing machinery. We propose that some of the oncogenic effects of YB-1 in breast cancer may be mediated through its interactions with sncRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Female
  • Humans
  • MCF-7 Cells
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Small Untranslated / genetics
  • RNA, Small Untranslated / metabolism*
  • Y-Box-Binding Protein 1 / genetics
  • Y-Box-Binding Protein 1 / metabolism*

Substances

  • Oncogene Proteins
  • RNA, Messenger
  • RNA, Small Untranslated
  • Y-Box-Binding Protein 1
  • YBX1 protein, human

Grant support

This work was funded by a research grant from The Genesis Oncology Trust, http://genesisoncology.org.nz/oncology/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.