C/D-box snoRNA-derived RNA production is associated with malignant transformation and metastatic progression in prostate cancer

  • Martens-Uzunova E
  • Hoogstrate Y
  • Kalsbeek A
 et al. 
  • 2

    Readers

    Mendeley users who have this article in their library.
  • N/A

    Citations

    Citations of this article.

Abstract

Small nucleolar RNAs (snoRNAs) are dynamically regulated in different tissues and affected in disease. SnoRNAs are processed further to stable smaller RNAs. We sequenced the small RNA transcriptome of prostate cancer (PCa) at different PCa stages and generated a quantified catalogue of 3927 small non-coding RNAs (sncRNAs) detected in normal and malignant prostate tissue. From these, only 1524 are microRNAs. The remaining 2401 sncRNAs represent stable sncRNAs species that originate from snoRNA, tRNA and other sncRNAs. We show that snoRNA-derived RNAs (sdRNAs) display stronger differential expression than microRNAs and are massively upregulated in PCa. SdRNAs account for at least one third of all small RNAs with expression changes in tumor compared to normal adjacent tissue. Multiple sdRNAs can be produced from one snoRNA in a manner related to the conservation of structural snoRNA motifs. Q-PCR analysis in an independent patient cohort (n=106) confirmed the processing patterns of selected snoRNAs (SNORD44, SNORD78, SNORD74 and SNORD81) and the cancer-associated up-regulation of their sdRNAs observed in sequencing data. Importantly, expression of SNORD78 and its sdRNA is significantly higher in a subset of patients that developed metastatic disease demonstrating that snoRNA and sdRNAs may present as novel diagnostic and/or prognostic biomarkers for PCa.

Author-supplied keywords

  • Cell Transformation, Neoplastic/*genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic/*genetics
  • Humans
  • Male
  • Neoplasm Invasiveness/*genetics/pathology
  • Prostatic Neoplasms/*genetics/*pathology
  • RNA, Small Nucleolar/*genetics
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Authors

  • E S Martens-Uzunova

  • Y Hoogstrate

  • A Kalsbeek

  • B Pigmans

  • M Vredenbregt-van den Berg

  • N Dits

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free