Elevated snoRNA biogenesis is essential in breast cancer

H. Su, T. Xu, S. Ganapathy, M. Shadfan, M. Long, T. H.M. Huang, I. Thompson, Z. M. Yuan

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

Hyperactive ribosomal biogenesis is widely observed in cancer, which has been partly attributed to the increased rDNA transcription by Pol I in cancer. However, whether small nucleolar RNAs (snoRNAs), a class of non-coding RNAs crucial in ribosomal RNA (rRNA) maturation and functionality, are involved in cancer remains elusive. We report that snoRNAs and fibrillarin (FBL, an enzymatic small nucleolar ribonucleoprotein, snoRNP) are frequently overexpressed in both murine and human breast cancer as well as in prostate cancers, and significantly, that this overexpression is essential for tumorigenicity in vitro and in vivo. We demonstrate that when the elevated snoRNA pathway is suppressed, the tumor suppressor p53 can act as a sentinel of snoRNP perturbation, the activation of which mediates the growth inhibitory effect. On the other hand, high level of FBL interferes with the activation of p53 by stress. We further show that p53 activation by FBL knockdown is not only regulated by the ribosomal protein-MDM2-mediated protein stabilization pathway, but also by enhanced PTB-dependent, cap-independent translation. Together, our data uncover an essential role of deregulated snoRNA biogenesis in tumors and a new mechanism of nucleolar modulation of p53.

Original languageEnglish (US)
Pages (from-to)1348-1358
Number of pages11
JournalOncogene
Volume33
Issue number11
DOIs
StatePublished - Mar 13 2014

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Keywords

  • breast cancer
  • fibrillarin
  • nucleolar stress
  • p53
  • snoRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Su, H., Xu, T., Ganapathy, S., Shadfan, M., Long, M., Huang, T. H. M., Thompson, I., & Yuan, Z. M. (2014). Elevated snoRNA biogenesis is essential in breast cancer. Oncogene, 33(11), 1348-1358. https://doi.org/10.1038/onc.2013.89