IDENTIFICATION OF LONG NON-CODING RNAs (lncRNAs) DYSREGULATED DURING PROSTATE CANCER PROGRESSION

OLSZEVICKI, SANTIAGO; COTIGNOLA, JAVIER; VAZQUEZ, ELBA; LEDESMA BAZÁN, SABRINA; GUERON, GERALDINE

Virtual

Congreso; Reunión Anual de la Sociedad Argentina de Investigación Clínica 2021; 2021

Most of the human genome is transcribed into non-coding RNAs which perform a myriad of tasks in cells. Their dysregulation is responsible of the development and progression of different pathological processes, including cancer. Prostate cancer is known for having a wide spectrum of clinical outcomes, ranging from an indolent tumor to a lethal metastatic castration resistant cancer (CRPC). But the biology of the processes leading to these phenotypes is still mostly unknown. The aim of this study was to identify lncRNAs involved in the progression of prostate tumors to CRPC. We browed public repositories and downloaded raw RNAseq data from primary prostate adenocarcinomas (pre- and post-androgen deprivation therapy (ADT); n=40 and n=11, respectively) and CRPC (n=8). We performed differential expression of 17,009 lncRNAs using R/Bioconductor. We identified 12 lncRNAs that responded to ADT and were further dysregulated in CRPC: PCA3, PCAT18, PCGEM1, LINC01095, GABRG3-AS1, HECW2-AS1, NKILA, LOC100506474, SLCA4-AS1, LOC101927870, LOC101929532, and LOC105377503. Interestingly, three of them were widely reported as players in prostate cancer development and progression, validating the pipeline used in this study. Unsupervised clustering analysis revealed that the 12-lncRNA-expression pattern could cluster post-ADT and CRPC samples apart. Primary tumors pre-ADT were more heterogeneous and clustered together with post-ADT or CRPC tumors. This suggests that primary prostate tumors that might potentially progress to CRPC could be detected at the time of diagnosis according to their lncRNA expression profile. In addition, we looked into promoter methylation of these lncRNAs in different types of tumors. Overall, we observed promoter hypomethylation in the tumors compared with normal counterpart. These results warrant further analysis in more samples and in-vitro experiments to validate the findings and determine the role of these lncRNAs in the pathogenesis of prostate cancer.