RGS12 is a novel tumor suppressor gene in African American prostate cancer that represses AKT and MNX1 expression

African American (AA) men exhibit a relatively high incidence and mortality due to prostate cancer (PCa) even after adjustment for socioeconomic factors, but the biological basis for this disparity is unclear. Here we identify a novel region on chromosome 4p16.3 that is lost selectively in AA PCa. The negative regulator of G-protein signaling RGS12 was defined as the target of 4p16.3 deletions, although it has not been implicated previously as a tumor suppressor gene. RGS12 transcript levels were relatively reduced in AA PCa and PCa cell lines showed decreased RGS12 expression relative to benign prostate epithelial cells. Notably, RGS12 exhibited potent tumor suppressor activity in PCa and prostate epithelial cell lines in vitro and in vivo. We found that RGS12 expression correlated negatively with the oncogene MNX1 and regulated its expression in vitro and in vivo. Further, MNX1 was regulated by AKT activity and RGS12 expression decreased total and activated AKT levels. Our findings identify RGS12 is a candidate tumor suppressor gene in AA PCa which acts by decreasing expression of AKT and MNX1, establishing a novel oncogenic axis in this disparate disease setting.

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