CONICET | Buscador de Institutos y Recursos Humanos

The human genome contains about 20,000 protein-coding genes, representing 2% of the genome. Historically, the other 98% of the genome was referred as junk DNA. However, there is now robust evidence that 85% of the genome can be transcribed and that approximately half of disease- and trait-associated genomic regions are intergenic. These non-protein-coding regions are transcribed to non-coding RNAs (ncRNA), which are known to be key regulators of the transcriptional and translational repertoire of the cell. Moreover, there are solid proofs that alterations of these ncRNAs are highly associated with tumor development and progression. Prostate cancer (PCa) is the second most incident type of cancer in men and the fifth leading cause of cancer-related deaths worldwide. However, the biology of PCa is still mostly unknown. Therefore, we aimed to identify long non-coding RNAs (lncRNAs) differentially expressed after androgen deprivation therapy (ADT). We downloaded raw transcriptome data from public repositories. The datasets comprise paired samples from PCa patients before and after ADT. We analyzed differential lncRNA expression using the algorithms edgeR and DESeq2 from R/Bioconductor. The lncRNAs were considered differentially expressed when there was an agreement between both algorithms and FDR-adjusted p-value|3| to further reduce the list and we identified 46 lncRNAs that met all three criteria. All of them are annotated in different genomic databases and 11/46 have been validated in different tumor samples including PCa, e.g.: PCAT18 (p=1.5e-28, Log2FC=-5), PCA3 (p=2.9e-10, Log2FC=-5) and PCGEM1 (p=1.2e-5, Log2FC=-7). Interestingly, all 46 lncRNAs were downregulated after ADT. This study revealed the lncRNAs modulated after ADT. These results warrant further investigation to give new insights in the biology of PCa and to identify potential therapeutic targets.