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

TY - JOUR

T1 - Prostate cancer downregulated SIRP-α modulates apoptosis and proliferation through p38-MAPK/NF-κB/COX-2 signaling

AU - Yao, Chen

AU - Li, Gang

AU - Cai, Ming

AU - Qian, Yeyong

AU - Wang, Liqin

AU - Xiao, Li

AU - Thaiss, Friedrich

AU - Shi, Bingyi

PY - 2017/6

Y1 - 2017/6

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.3892/ol.2017.6070

DO - 10.3892/ol.2017.6070

M3 - SCORING: Journal article

C2 - 28588738

VL - 13

SP - 4995

EP - 5001

JO - ONCOL LETT

JF - ONCOL LETT

SN - 1792-1074

IS - 6

ER -