siRNA Knockdown of Ribosomal Protein Gene RPL19 Abrogates the Aggressive Phenotype of Human Prostate Cancer

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.

rpL3 promotes the apoptosis of p53 mutated lung cancer cells by down-regulating CBS and NFκB upon 5-FU treatment

“…rpS2 was reported to be a therapeutic targeting for the eradication of prostate cancer in preclinical tumor modeling studies31. Silencing of rpL19 abrogated the aggressive phenotype of human prostate cancer32.…”

Disruption of the ribosomal P complex leads to stress-induced autophagy

“…These RPLP protein-deficient cells have high levels of intracellular ROS, and it is recognized that deregulation of the cellular redox state can impact the levels and activity of TP53. 51,52 Higher levels of ROS appear to be part of a feed-forward loop that stabilizes TP53, which may occur in MCF-7 cells treated with 3-MA, resulting in increased TP53 activity that interferes with mitochondrial function and/or integrity, and eventually contributes to cell death. 53 Recent research reveals that autophagy is activated by TP53 and members of the MAPK11/12/13/14 family.…”

Over-expressed RPL34 promotes malignant proliferation of non-small cell lung cancer cells

“…And the secretion was positively correlative with degree of drug-resistance and malignance of cancer cells (Kim et al, 2013). RPL19 was highly expressed in some prostate cancers and colorectal cancers, and it was studied as a prognostic biomarker for these two cancers (Bee et al, 2011;Yang et al, 2010;Huang et al, 2008;Bee et al, 2006). In addition, RPS15A (Xu et al, 2013), RPL26 and RPL29 (Li et al, 2012) were also found to be associated with cancer cells proliferation.…”