siRNA knockdown of ribosomal protein gene RPL19 abrogates the aggressive phenotype of human prostate cancer

Bee, Alix, Brewer, Daniel ORCID: https://orcid.org/0000-0003-4753-9794, Beesley, Carol, Dodson, Andrew, Forootan, Shiva, Dickinson, Timothy, Gerard, Patricia, Lane, Brian, Yao, Sheng, Cooper, Colin S. ORCID: https://orcid.org/0000-0003-2013-8042, Djamgoz, Mustafa B. A., Gosden, Christine M., Ke, Youqiang and Foster, Christopher S. (2011) siRNA knockdown of ribosomal protein gene RPL19 abrogates the aggressive phenotype of human prostate cancer. PLoS One, 6 (7). ISSN 1932-6203

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Abstract

We provide novel functional data that posttranscriptional silencing of gene RPL19 using RNAi not only abrogates the malignant phenotype of PC-3M prostate cancer cells but is selective with respect to transcription and translation of other genes. Reducing RPL19 transcription modulates a subset of genes, evidenced by gene expression array analysis and Western blotting, but does not compromise cell proliferation or apoptosis in-vitro. However, growth of xenografted tumors containing the knocked-down RPL19 in-vivo is significantly reduced. Analysis of the modulated genes reveals induction of the non-malignant phenotype principally to involve perturbation of networks of transcription factors and cellular adhesion genes. The data provide evidence that extra-ribosomal regulatory functions of RPL19, beyond protein synthesis, are critical regulators of cellular phenotype. Targeting key members of affected networks identified by gene expression analysis raises the possibility of therapeutically stabilizing a benign phenotype generated by modulating the expression of an individual gene and thereafter constraining a malignant phenotype while leaving non-malignant tissues unaffected.

Item Type:	Article
Additional Information:	© 2011 Bee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Uncontrolled Keywords:	base sequence,cell line, tumor,cell proliferation,gene expression profiling,gene knockdown techniques,humans,male,molecular targeted therapy,phenotype,prostatic neoplasms,rna interference,rna, small interfering,ribosomal proteins,transfection,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User:	Pure Connector
Date Deposited:	06 Jan 2014 14:16
Last Modified:	19 Oct 2023 01:13
URI:	https://ueaeprints.uea.ac.uk/id/eprint/46125
DOI:	10.1371/journal.pone.0022672

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