Links between the Oncoprotein YB-1 and Small Non-Coding RNAs in Breast Cancer

Abstract

BackgroundThe 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.ResultsRNA-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.ConclusionsYB-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.

Identification of urinary exosomal noncoding RNAs as novel biomarkers in chronic kidney disease

“…Recent reports imply that YBX1 is required for loading of various RNA species, including tRFs, into exosomes (Shurtleff et al 2016). Some studies have reported that YBX1 binds to several RNAs like tRNA fragments and miRNAs (Blenkiron et al 2013;Goodarzi et al 2015;Liu et al 2015). In the present study, we found significant changes in exosomal tRFs and observed an increase in healthy controls, compared to CKD patients, which were derived from the 5 ′ end of the mature tRNAs (Fig.…”

Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction

“…Our studies focused on miRNAs, however it is possible that YBX1 is responsible for the secretion of other RNA classes in exosomes. Several recent reports indicate a role for YBX1 in binding various small RNAs, including miRNAs, tRNA fragments and snoRNAs (Blenkiron, Hurley, Fitzgerald, Print, & Lasham, 2013;Goodarzi et al, 2015;. It is interesting to note that most miRNAs present in exosomes in our study are not highly enriched compared to their relative abundance in cells.…”

Discovery and function of transfer RNA‐derived fragments and their role in disease

“…Angiogenin, which catalyses stress‐induced tRF biogenesis is also consistently up‐regulated in different cancers, where hypoxia is a major stress factor, suggesting that stress‐induced tRFs may be involved in carcinogenesis. In breast cancer, tRFs are found associated with oncoprotein YB‐1, a driver of breast cancer in vivo , which is up‐regulated in a wide variety of cancers. Both stress‐dependent 5′ tRFs and YB‐1 are found in SG and tRFs associated with YB‐1 are involved in translation repression as stated above .…”

“…For example, tRFs have been found in respiratory syncytial virus (RSV), HIV, and human T‐cell lymphotropic virus (HTLV‐1) infected cells . Different tRFs have been implicated in cellular proliferation and tRF signatures are being described in different types of cancer . In this review, we describe the different sub‐classes of tRFs and discuss their functions and their relevance to human disease.…”