Genes regulated by soluble guanylyl cyclase in VCaP prostate cancer cells

The aberrant activation of the ERG oncogenic pathway due to TMPRSS2-ERG gene fusions is the major driver of prostate cancer initiation and progression. We identified the alpha1 and beta1 subunits of soluble guanylyl cyclase (GUCY1A1, GUCY1B1) as major ERG-regulated genes in prostate cancer cells. Soluble guanylyl cyclase (sGC) is the major mediator of nitric oxide signaling in cells that, upon nitric oxide binding, catalyzes the synthesis of cGMP and subsequently activates PKG. We showed in ERG-positive PCa cells (VCaP) that cGMP synthesis was significantly elevated by ERG, leading to increased PKG activity and cell proliferation. To further understand the functions of sGC-cGMP pathway in prostate cancer cells, we performed RNA-seq analyses in VCaP cells to identify genes that are regulated by sGC. Firstly, we performed RNA-seq analyses to examine genes differentially regulated by alpha1 or beta1 subunit of sGC in VCaP cells transfected with siRNA against non-target-control (siNTC), GUCY1A1 (siGUCY1A1), or GUCY1B1 (siGUCY1B1). Secondly, we also performed RNA-seq to examine the gene expression profile in VCaP cells treated with vehicle or ODQ, an sGC inhibitor that blocks cGMP synthesis.