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

Yao,Chen; Li,Gang; Cai,Ming; Qian,Yeyong; Wang,Liqin; Xiao,Li; Thaiss,Friedrich; Shi,Bingyi

doi:10.3892/ol.2017.6070

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

Authors:
- Chen Yao
- Gang Li
- Ming Cai
- Yeyong Qian
- Liqin Wang
- Li Xiao
- Friedrich Thaiss
- Bingyi Shi
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Affiliations: Organ Transplant Institute, Chinese People's Liberation Army 309th Hospital, Beijing 100091, P.R. China, III Medical Clinic, University Hospital, Eppendorf, D‑20246 Hamburg, Germany
Published online on: April 21, 2017 https://doi.org/10.3892/ol.2017.6070
Pages: 4995-5001

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Abstract

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.

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