2. Academic Validation
  3. Non-coding RNAs derived from an alternatively spliced REST transcript (REST-003) regulate breast cancer invasiveness

Non-coding RNAs derived from an alternatively spliced REST transcript (REST-003) regulate breast cancer invasiveness

  • Sci Rep. 2015 Jun 8;5:11207. doi: 10.1038/srep11207.
Nan Sook Lee 1,  Oleg V Evgrafov 2,  Tade Souaiaia 2,  Adrineh Bonyad 3,  Jennifer Herstein 2,  Joo Yeun Lee 4,  Jihong Kim 2,  Yan Ning 5,  Marcos Sixto 6,  Andrew C Weitz 7,  Heinz-Josef Lenz 5,  Kai Wang 2,  James A Knowles 2,  Michael F Press 8,  Paul M Salvaterra 9,  K Kirk Shung 10,  Robert H Chow 3
Affiliations

Affiliations

  • 1 1] Physiology &Biophysics and Zilkha Neurogenetic Institute, University of Southern California, Los Angeles [2] Dept of Biomedical Engineering, University of Southern California, Los Angeles.
  • 2 Psychiatry &the Behavioral Sciences, University of Southern California, Los Angeles.
  • 3 Physiology &Biophysics and Zilkha Neurogenetic Institute, University of Southern California, Los Angeles.
  • 4 Neuroscience Graduate Program, University of Southern California, Los Angeles.
  • 5 Dept of Medicine, Norris Cancer Center, University of Southern California, Los Angeles.
  • 6 Pasadena City College, Pasadena.
  • 7 Dept of Ophthalmology, University of Southern California, Los Angeles, CA.
  • 8 Dept of Pathology, Norris Cancer Center, University of Southern California, Los Angeles.
  • 9 Department of Neuroscience, Beckman Research Institute of the City of Hope, Duarte, CA.
  • 10 Dept of Biomedical Engineering, University of Southern California, Los Angeles.
PMID: 26053433 DOI: 10.1038/srep11207
Abstract

RE1-Silencing Transcription factor (REST) has a well-established role in regulating transcription of genes important for neuronal development. Its role in Cancer, though significant, is less well understood. We show that REST downregulation in weakly invasive MCF-7 breast Cancer cells converts them to a more invasive phenotype, while REST overexpression in highly invasive MDA-MB-231 cells suppresses invasiveness. Surprisingly, the mechanism responsible for these phenotypic changes does not depend directly on the transcriptional function of REST protein. Instead, it is driven by previously unstudied mid-size (30-200 nt) non-coding RNAs (ncRNAs) derived from the first exon of an alternatively spliced REST transcript: REST-003. We show that processing of REST-003 into ncRNAs is controlled by an uncharacterized serine/arginine repeat-related protein, SRRM3. SRRM3 expression may be under REST-mediated transcriptional control, as it increases following REST downregulation. The SRRM3-dependent regulation of REST-003 processing into ncRNAs has many similarities to recently described promoter-associated small RNA-like processes. Targeting ncRNAs that control invasiveness could lead to new therapeutic approaches to limit breast Cancer metastasis.

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