Messenger RNAs under Differential Translational Control in Ki-ras-Transformed Cells

Sidney Kimmel Cancer Center, San Diego, CA, USA.
Molecular Cancer Research (Impact Factor: 4.38). 02/2006; 4(1):47-60. DOI: 10.1158/1541-7786.MCR-04-0187
Source: PubMed


Microarrays have been used extensively to identify differential gene expression at the level of transcriptional control in oncogenesis. However, increasing evidence indicates that changes in translational control are critical to oncogenic transformation. This study identifies mRNA transcripts that are differentially regulated, primarily at the level of translation, in the immortalized human embryonic prostate epithelial cell line 267B1 and the v-Ki-ras-transformed counterpart by comparing total mRNA to polysome-bound mRNA by using Affymetrix oligonucleotide microarrays. Among the transcripts that were identified were those encoding proteins involved in DNA replication, cell cycle control, cell-to-cell interactions, electron transport, G protein signaling, and translation. Many of these proteins are known to contribute to oncogenesis or have the potential to contribute to oncogenesis. Differential expression of RNA-binding proteins and the presence of highly conserved motifs in the 5' and 3' untranslated regions of the mRNAs are consistent with multiple pathways and mechanisms governing the changes in translational control. Although Alu sequences were found to be associated with increased translation in transformed cells, an evolutionarily conserved motif was identified in the 3' untranslated regions of ephrinB1, calreticulin, integrin alpha3, and mucin3B that was associated with decreased polysome association in 267B1/Ki-ras.

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    • "Extensive efforts are being made to discover more cis‐regulatory elements by identifying new RBPs (Castello et al, 2013) and characterizing their binding sites (Hafner et al, 2010). Such studies are gaining momentum, especially in light of an increasing number of RBPs emerging as oncogenes (Spence et al, 2006) that exert effects on post‐transcriptional phenotypes. The methods established in this study can be applied to investigate the regulatory potential of these new RBPs. "
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