3.9 Article

High-grade ovarian cancer associated H/ACA snoRNAs promote cancer cell proliferation and survival

期刊

NAR CANCER
卷 4, 期 1, 页码 -

出版社

OXFORD UNIV PRESS
DOI: 10.1093/narcan/zcab050

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资金

  1. Canadian Institutes of Health Research (CIHR) [PJT 153171]
  2. CRCHUS (PAFI program)
  3. Canada Research Chair in RNA Biology and Cancer Genomics
  4. Fonds de Recherche du Quebec -Sante (FRQS) Research Scholar Senior Career Award
  5. FRQS
  6. CIHR
  7. NSERC CREATE, RNA innovation program
  8. NSERC
  9. NIH [R01 GM37949, R35 GM136216]

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This study accurately surveyed the abundance of snoRNAs in ovarian cancer tissues using a sensitive sequencing technique. Several specific snoRNAs were identified, which may promote tumor aggressiveness by inducing rRNA modification and synthesis.
Small nucleolar RNAs (snoRNAs) are an omnipresent class of non-coding RNAs involved in the modification and processing of ribosomal RNA (rRNA). As snoRNAs are required for ribosome production, the increase of which is a hallmark of cancer development, their expression would be expected to increase in proliferating cancer cells. However, assessing the nature and extent of snoRNAs' contribution to cancer biology has been largely limited by difficulties in detecting highly structured RNA. In this study, we used a dedicated midsize non-coding RNA (mncRNA) sensitive sequencing technique to accurately survey the snoRNA abundance in independently verified high-grade serous ovarian carcinoma (HGSC) and serous borderline tumour (SBT) tissues. The results identified SNORA81, SNORA19 and SNORA56 as an H/ACA snoRNA signature capable of discriminating between independent sets of HGSC, SBT and normal tissues. The expression of the signature SNORA81 correlates with the level of ribosomal RNA (rRNA) modification and its knockdown inhibits 28S rRNA pseudouridylation and accumulation leading to reduced cell proliferation and migration. Together our data indicate that specific subsets of H/ACA snoRNAs may promote tumour aggressiveness by inducing rRNA modification and synthesis.

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