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.
Highlights
Malignant transformation and cancer progression cause changes in the expression and function of microRNAs [1, 2]
It is generally accepted that small nucleolar RNAs are housekeeping, protein-noncoding molecules that associate with specific sets of proteins to maintain proper ribosomal maturation in the nucleolus
The correct mapping of small non-coding RNAs (sncRNAs) reads is challenged by the fact that predominant isoforms of miRNAs and other sncRNAs such as small nucleolar RNAs (snoRNAs) may vary from the mature sequences annotated in public databases
Summary
Malignant transformation and cancer progression cause changes in the expression and function of microRNAs (miRNAs) [1, 2]. We demonstrated the abundance and differential expression of small nucleolar RNA-derived RNAs (sdRNAs) in the small transcriptome of prostate cancer (PCa) [3]. It is generally accepted that small nucleolar RNAs (snoRNAs) are housekeeping, protein-noncoding molecules that associate with specific sets of proteins to maintain proper ribosomal maturation in the nucleolus. Several reports show that snoRNAs have tissue-specific expression [4, 5], and may present as novel cancer biomarkers. The H/ACAbox snoRNA SNORA42 is commonly overexpressed in non-small cell lung cancer (NSCLC) and its expression is significantly inversely correlated with survival [6, 7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
