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Mol Oncol. 2016 May;10(5):693-703. doi: 10.1016/j.molonc.2015.12.010. Epub 2015 Dec 22.

Integrated analysis of the prostate cancer small-nucleolar transcriptome reveals SNORA55 as a driver of prostate cancer progression.

Author information

1
Experimental Therapeutics, BC Cancer Agency Cancer Research Centre, Vancouver BC, Canada; The Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver BC, Canada; Department of Life, Health, and Chemical Sciences, The Open University, Milton Keynes, UK.
2
Molecular Pathology Unit, Institute of Pathology University Hospital Basel, Switzerland.
3
Oncology, FHMS, School of Biosciences and Medicine, University of Surrey, UK.
4
Experimental Therapeutics, BC Cancer Agency Cancer Research Centre, Vancouver BC, Canada.
5
Karolinska Institutet, Institute of Environmental Medicine, Unit of Biostatistics, Stockholm, Sweden.
6
Medical Oncology, BC Cancer Agency Vancouver Cancer Centre, Vancouver BC, Canada.
7
Genetics Unit, Integrative Oncology, BC Cancer Agency Cancer Research Centre, Vancouver BC, Canada.
8
Experimental Therapeutics, BC Cancer Agency Cancer Research Centre, Vancouver BC, Canada; The Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver BC, Canada.
9
Cancer Center ZeTuP AG St.Gallen, St.Gallen, Switzerland.
10
Integrated DNA Technologies, Coralville, IA, USA.
11
The Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver BC, Canada.
12
The Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver BC, Canada; Medical Oncology, BC Cancer Agency Vancouver Cancer Centre, Vancouver BC, Canada.
13
Experimental Therapeutics, BC Cancer Agency Cancer Research Centre, Vancouver BC, Canada; The Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver BC, Canada. Electronic address: ywang@bccrc.ca.
14
Experimental Therapeutics, BC Cancer Agency Cancer Research Centre, Vancouver BC, Canada. Electronic address: chelgaso@bccrc.ca.

Abstract

Metastasis is the primary cause of death in prostate cancer (PCa) patients. Small nucleolar RNAs (snoRNAs) have long been considered "housekeeping" genes with no relevance for cancer biology. Emerging evidence has challenged this assumption, suggesting that snoRNA expression is frequently modulated during cancer progression. Despite this, no study has systematically addressed the prognostic and functional significance of snoRNAs in PCa. We performed RNA Sequencing on paired metastatic/non-metastatic PCa xenografts derived from clinical specimens. The clinical significance of differentially expressed snoRNAs was further investigated in two independent primary PCa cohorts (131 and 43 patients, respectively). The snoRNA demonstrating the strongest association with clinical outcome was quantified in PCa patient-derived serum samples and its functional relevance was investigated in PCa cells via gene expression profiling, pathway analysis and gene silencing. Our comparison revealed 21 differentially expressed snoRNAs in the metastatic vs. non-metastatic xenografts. Of those, 12 were represented in clinical databases and were further analyzed. SNORA55 emerged as a predictor of shorter relapse-free survival (results confirmed in two independent databases). SNORA55 was reproducibly detectable in serum samples from PCa patients. SNORA55 silencing in PCa cell lines significantly inhibited cell proliferation and migration. Pathway analysis revealed that SNORA55 expression is significantly associated with growth factor signaling and pro-inflammatory cytokine expression in PCa. Our results demonstrate that SNORA55 up-regulation predicts PCa progression and that silencing this non-coding gene affects PCa cell proliferation and metastatic potential, thus positioning it as both a novel biomarker and therapeutic target.

KEYWORDS:

Antisense oligonucleotide; Next generation sequencing; Non-coding RNAs; Patient-derived xenograft; Prostate cancer; SNORA55

PMID:
26809501
PMCID:
PMC5423162
DOI:
10.1016/j.molonc.2015.12.010
[Indexed for MEDLINE]
Free PMC Article

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