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

Francesco Crea, Luca Quagliata, Agnieszka Michael, Hui Hsuan Rebecca Liu, Paolo Frumento, Arun A Azad, Hui Xue, Larissa A Pikor, Akira Watahiki, Rudolf Morant, Serenella Eppenberger-Castori, Yuwei Wang, Abhijit Parolia, Kim A Lennox, Wan L Lam, Martin E Gleave, Kim N Chi, Hardev S Pandha, Yuzhuo Wang, Cheryl D Helgason

Research output: Contribution to journalArticleResearchpeer-review

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.
Original languageEnglish
Pages (from-to)693-703
Number of pages11
JournalMolecular Oncology
Volume10
Issue number5
DOIs
Publication statusPublished - May 2016
Externally publishedYes

Keywords

  • Prostate cance
  • SNORA55
  • Non-coding RNAs
  • Patient-derived xenograft
  • Next generation sequencing
  • Antisense oligonucleotide

Cite this

Crea, Francesco ; Quagliata, Luca ; Michael, Agnieszka ; Liu, Hui Hsuan Rebecca ; Frumento, Paolo ; Azad, Arun A ; Xue, Hui ; Pikor, Larissa A ; Watahiki, Akira ; Morant, Rudolf ; Eppenberger-Castori, Serenella ; Wang, Yuwei ; Parolia, Abhijit ; Lennox, Kim A ; Lam, Wan L ; Gleave, Martin E ; Chi, Kim N ; Pandha, Hardev S ; Wang, Yuzhuo ; Helgason, Cheryl D. / Integrated analysis of the prostate cancer small-nucleolar transcriptome reveals SNORA55 as a driver of prostate cancer progression. In: Molecular Oncology. 2016 ; Vol. 10, No. 5. pp. 693-703.
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title = "Integrated analysis of the prostate cancer small-nucleolar transcriptome reveals SNORA55 as a driver of prostate cancer progression",
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 = "Prostate cance, SNORA55, Non-coding RNAs, Patient-derived xenograft, Next generation sequencing, Antisense oligonucleotide",
author = "Francesco Crea and Luca Quagliata and Agnieszka Michael and Liu, {Hui Hsuan Rebecca} and Paolo Frumento and Azad, {Arun A} and Hui Xue and Pikor, {Larissa A} and Akira Watahiki and Rudolf Morant and Serenella Eppenberger-Castori and Yuwei Wang and Abhijit Parolia and Lennox, {Kim A} and Lam, {Wan L} and Gleave, {Martin E} and Chi, {Kim N} and Pandha, {Hardev S} and Yuzhuo Wang and Helgason, {Cheryl D}",
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Crea, F, Quagliata, L, Michael, A, Liu, HHR, Frumento, P, Azad, AA, Xue, H, Pikor, LA, Watahiki, A, Morant, R, Eppenberger-Castori, S, Wang, Y, Parolia, A, Lennox, KA, Lam, WL, Gleave, ME, Chi, KN, Pandha, HS, Wang, Y & Helgason, CD 2016, 'Integrated analysis of the prostate cancer small-nucleolar transcriptome reveals SNORA55 as a driver of prostate cancer progression' Molecular Oncology, vol. 10, no. 5, pp. 693-703. https://doi.org/10.1016/j.molonc.2015.12.010

Integrated analysis of the prostate cancer small-nucleolar transcriptome reveals SNORA55 as a driver of prostate cancer progression. / Crea, Francesco; Quagliata, Luca; Michael, Agnieszka; Liu, Hui Hsuan Rebecca; Frumento, Paolo; Azad, Arun A; Xue, Hui; Pikor, Larissa A; Watahiki, Akira; Morant, Rudolf; Eppenberger-Castori, Serenella; Wang, Yuwei; Parolia, Abhijit; Lennox, Kim A; Lam, Wan L; Gleave, Martin E; Chi, Kim N; Pandha, Hardev S; Wang, Yuzhuo; Helgason, Cheryl D.

In: Molecular Oncology, Vol. 10, No. 5, 05.2016, p. 693-703.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Integrated analysis of the prostate cancer small-nucleolar transcriptome reveals SNORA55 as a driver of prostate cancer progression

AU - Crea, Francesco

AU - Quagliata, Luca

AU - Michael, Agnieszka

AU - Liu, Hui Hsuan Rebecca

AU - Frumento, Paolo

AU - Azad, Arun A

AU - Xue, Hui

AU - Pikor, Larissa A

AU - Watahiki, Akira

AU - Morant, Rudolf

AU - Eppenberger-Castori, Serenella

AU - Wang, Yuwei

AU - Parolia, Abhijit

AU - Lennox, Kim A

AU - Lam, Wan L

AU - Gleave, Martin E

AU - Chi, Kim N

AU - Pandha, Hardev S

AU - Wang, Yuzhuo

AU - Helgason, Cheryl D

PY - 2016/5

Y1 - 2016/5

N2 - 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.

AB - 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.

KW - Prostate cance

KW - SNORA55

KW - Non-coding RNAs

KW - Patient-derived xenograft

KW - Next generation sequencing

KW - Antisense oligonucleotide

U2 - 10.1016/j.molonc.2015.12.010

DO - 10.1016/j.molonc.2015.12.010

M3 - Article

VL - 10

SP - 693

EP - 703

JO - Molecular Oncology

JF - Molecular Oncology

SN - 1574-7891

IS - 5

ER -