The role and mechanism of PILRB in promoting prostate cancer progression by regulating CCL2 and CCL5 secretion

doi:10.3969/j.issn.1006-7795.2026.02.014

Abstract

Abstract: Objective To investigate the expression of paired immunoglobin like type 2 receptor beta (PILRB) in prostate cancer (PCa), and to evaluate its effects on the proliferation, migration, as well as the underlying mechanisms. Methods Small interfering RNA (siRNA) was used to knock down PILRB expression in prostate cancer cells. Quantitative real-time polymerase chain reaction (qPCR) was performed to verify the mRNA expression level. Immunohistochemistry (IHC) staining and Western blotting(WB) were employed to detect the expression of PILRB and related proteins. Cell counting kit-8 (CCK-8) assay, scratch wound healing assay, immunofluorescent staining (IF) and Transwell chamber assay were conducted to assess the proliferation, migration, and invasion capabilities of prostate cancer cells in vitro. The tumor-promoting role of PILRB in vivo was investigated using immunodeficient nude mice. Results PILRB protein expression was notably elevated in PCa tissues exhibiting high Gleason scores relative to those with low scores. Suppression of PILRB expression markedly inhibited the proliferation （22RV1：1.054±0.054 vs 1.959±0.032，t=40.574，P＜0.001；PC3：1.606±0.535 vs 2.178±0.479，t=22.497，P＜0.01；DU145：1.290±0.184 vs 2.147±0.597，t=38.750，P＜0.01）, transwell invasion assay (unit：n per field) （siPILRB-2：11.500±3.271 vs 101.667±12.909，t=16.584，P＜0.001） and migration （siPILRB-2：67.125±1.178 vs 81.588±1.454，t=21.855，P＜0.001；si-CCL2：63.100±3.019 vs 81.588±1.454，t=15.602，P＜0.001） of prostate cancer cells in vitro. Knockdown of PILRB effectively suppressed the secretion of C-C motif chemokine ligand 2 (CCL2） and C-C motif chemokine ligand 5 (CCL5） (pg/mL), as determined by ELISA （CCL2：82.450±3.075 vs 92.061±4.925，t=4.966，P＜0.01；CCL5：796.558±11.606 vs 816.300±19.965，t=2.564，P＜0.05；CSF-1：92.771±5.276 vs 106.787±10.016，t=3.714，P＜0.05）. This finding was further supported at the intracellular relative protein expression level by WB, which showed a significant downregulation of CCL2 （PILRB：0.305±0.007 vs 0.706±0.016，t=54.668，P＜0.05；CCL2：0.149±0.005 vs 0.522±0.204，t=43.221，P＜0.05）and a modest decrease in CCL5 （CCL5：0.204±0.005 vs 0.220±0.014，t=2.468，P＜0.05）in siPILRB-2-transfected cells relative to the si-Control. Subcutaneous xenograft tumors formed from PILRB-knockdown cells displayed significantly reduced tumor volumes in vivo （shPILRB：585.920±117.582 vs.1 314.462±234.633，t=6.207，P＜0.001）. Conclusion Elevated expression of PILRB in prostate cancer cells promotes the progression of prostate cancer by enhancing the secretion of CCL2 and CCL5, which modulates the differentiation of monocytes and macrophages towards the M2 phenotype. Therefore, PILRB may serve as a potential therapeutic target for suppressing prostate cancer progression.

Key words: prostate cancer, PILRB, CCL2, CCL5, proliferation and migration, immunohistochemistry, in vivo

CLC Number:

R737.25

Lü Suzhan, Zou Fan, Zhang Yishan, Wang Mingdong, Quan Yongjun, Ping Hao. The role and mechanism of PILRB in promoting prostate cancer progression by regulating CCL2 and CCL5 secretion[J]. Journal of Capital Medical University, 2026, 47(2): 326-337.

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