. IMPLICATIONS OF HEMEOXYGENASE 1 MODULATION OF INTERFERON INDUCIBLE ANTIVIRAL (MX1) IN PROSTATE CANCER

VALACCO, MARIA PIA; PAEZ ALEJANDRA V.; GUERON, GERALDINE; COTIGNOLA JAVIER; ORTIZ EMILIANO G.; VAZQUEZ ELBA S.; ANSELMINO NICOLAS

Buenos Aires

Congreso; LXXII Reunón Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2017

SAIC

The principal goal currently within prostate cancer (PCa) research is to unveilmarkers for early detection of aggressive tumors that are predestined to invadeand metastasize. We have previously reported that heme oxygenase-1 (HO-1)exerts an anti-tumoral role in PCa, ascertaining it as a logical target for therapyintervention. Considering the cross talk between inflammation and cancerprogression, our next step sought to identify signaling pathways by which HO-1could be operating. Towards this end we performed and analyzed RNAseq data onPCa cells overexpressing HO-1 pharmacologically or genetically. Of note HO-1significantly up-regulated the human myxovirus resistant protein A (Mx1). In vitrostudies revealed that forced expression of HO-1 in PCa cells, significantly up-regulated MX1 mRNA and protein levels and shifted its localization towards theperinuclear area.To address the relevance of MX1 in PCa we searched the public cancer microarraydatabase, Oncomine. MX1 was ranked by its P-value for every analysis scoring agene rank. We then obtained a median rank (Median P-value rank acrossdatasets) for MX1. The expression profile for MX1 showed a significant down-regulation (fold change 1.5, P0.05) comparing prostate adenocarcinoma vs.normal prostate gland, lying within the 2-19 % of the most consistently low-expressed genes across this comparison.We extended the bioinformatics analysis, using cBioportal, assesing whole exomeand RNAseq data. The most frequent genetic alteration found for MX1 wasdeletion. RNASeq data also confirmed a significant down-regulation for MX1(P0.05). Moreover, Kaplan-Meier analysis also showed in PCa patients that MX1loss was associated with decreased overall and disease-free survival (P0.05).Overall, HO-1 potentially operates through Mx1, whose expression inverselycorrelates with PCa, depicting its critical role in prostate carcinogenesis.