Implications of heme-oxygenase 1 modulation of interferon inducible antiviral (MX1) in prostate cancer

PAEZ, ALEJANDRA; VALACCO, PIA; ORTIZ, EMILIANO; COTIGNOLA, JAVIER; GUERON, GERALDINE; ANSELMINO, NICOLAS; VAZQUEZ, ELBA

CABA

Congreso; Reunión Conjunta de Sociedades de BioCiencias - LXII Reunion Anual SAIC; 2017

Sociedad Argentina de Investigacion Clinica

The principal goal currently within prostate cancer (PCa) research is to unveil markers for early detection of aggressive tumors that are predestined to invade and 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 therapy intervention. HO-1 over-expression impairs tumor growth and angiogenesis invivo. Considering the cross talk between inflammation, angiogenesis and cancer progression, our next step sought to identify signaling pathways by which HO-1 could be operating. Towards this end we performed and analysed RNAseq data on PCa cells overexpressing HO-1 pharmacologically or genetically. Of note HO-1 significantly up-regulated the human myxovirus resistant protein A (Mx1). In vitro studies revealed that forced expression of HO-1 in PCa cells, significantlyup-regulated MX1 mRNA and protein levels and shifted its localization towards the perinuclear area. To address the relevance of MX1 in PCa we searched the public cancer microarray database, Oncomine. MX1 was ranked by its P-value for every analysis scoring a gene rank. We then obtained a median rank (Median P-value rank across datasets) for MX1. The expression profile for MX1 showed a significant down-regulation (fold change 1.5, P