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

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.

• Authors: Cherie Blenkiron, Daniel G Hurley, Sandra Fitzgerald, Cristin G Print, Annette Lasham
• Journal: PloS one (PLoS One) Vol. 8 Issue 11 Pg. e80171 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24260353 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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