Prostate cancer downregulated SIRP-α modulates apoptosis and proliferation through p38-MAPK/NF-κB/COX-2 signaling.

The present study investigated the regulatory mechanism of signal-regulatory protein (SIRP)-α in the apoptosis and proliferation of prostate cancer (CaP) cells. The expression profile of SIRP-α in prostate cancer cells was analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting. Then SIRP-α function in CaP cells was further analyzed with the overexpression and RNA interference of SIRP-α. The results revealed that SIRP-α expression levels were decreased in CaP tissues and cell lines, with androgen-independent CaP exhibiting a lower SIRP-α expression compared with androgen-dependent CaP. Overexpression of SIRP-α resulted in a significantly reduced number of live CaP cells by enhancing apoptosis, whereas SIRP-α silencing increased CaP cell proliferation. Mechanistically, SIRP-α decreases cyclooxygenase-2 (COX-2) expression and cytokine production by negatively regulating p38 mitogen-activated protein kinase and nuclear factor-κB pathway. Therefore, SIRP-α knockdown decreases cell apoptosis by enhancing COX-2 expression. The present results indicate that SIRP-α may function as a novel negative regulator to modulate cellular proliferation, survival and migration in CaP cells. The heightened sensitivity of cells restoring SIRP-α function could be exploited in the development of therapeutics that may potentiate the antineoplastic effects of conventional cytokines or chemotherapeutic agents.