Prostate cancer resistance leads to a global deregulation of translation factors and unconventional translation

Using a newly generated enzalutamide-resistant prostate cancer model, we characterized alterations in the translatome during prostate cancer enzalutamide resistance acquisition. We show a discordance between the translatome and transcriptome of drug-resistant cells, a deregulation of proteins involved in translation and an overall decrease in translational efficiency upon resistance acquisition. Interestingly, long non-coding RNAs show higher translation efficiency in enzalutamide-resistant cells, and a strong correlation with poor patient prognosis. Taken together, this suggests that aberrant translation of coding and non-coding genes are strong indicators of PCa enzalutamide-resistance. RNA sequencing of Poly(A) RNA from enzalutamide sensitive VCaP and VCaP-CRPC (Castration Resistant Prostate Cancer) and of enzalutamide resistant VCaP-ER (Enzalutamide Resistant), and RNA sequencing of heavy polysome-bound RNA from VCaP-CRPC and VCaP-ER (as duplicates).