Copine 1 predicts poor clinical outcomes by promoting M2 macrophage activation in ovarian cancer.
Bo ShengBo ZhaoYue DongJiamin ZhangSuni WuHuihui JiXueqiong ZhuPublished in: Carcinogenesis (2023)
Copine 1 (CPNE1), a membrane-binding protein, influences the prognosis of various cancers. According to cBioPortal, CPNE1 amplification is a prevalent genetic mutation in ovarian cancer but with unknown oncogenic mechanism. This study analysed the CPNE1 expression in ovarian cancer using online datasets, as validated by immunohistochemistry (IHC), quantitative polymerase chain reaction (qPCR) and Western blotting. Concurrently, the prognostic value of CPNE1 was accessed. Cell Counting Kit-8, colony formation, transwells and xenograft experiments were performed to evaluate the functions of CPNE1 during ovarian cancer carcinogenesis. CPNE1 and its related genes were analyzed by g:Profiler and Tumour Immune Estimation Resource. Furthermore, THP-1 cells were co-cultured with ES2 cells to investigate the effect of CPNE1 on macrophage polarisation. The results of bioinformatic analysis, IHC, qPCR and Western blotting indicated a higher CPNE1 in ovarian cancer. CPNE1 overexpression demonstrated an association with a poor prognosis of ovarian cancer. Functionally, CPNE1 overexpression increased ES2 and SKOV3 cell proliferation, invasion and migration in vitro and promoted ovarian tumour xenograft growth in vivo, while CPNE1 knockdown led to opposite effects. Additionally, CPNE1 expression demonstrated an association with immune cell infiltration in ovarian cancer, especially macrophage. CPNE1 promoted pro-tumour M2 macrophage polarisation by upregulating cluster of differentiation (CD) 163, CD206 and interleukin-10. Our study revealed that CPNE1 mediated M2 macrophage polarisation and provided a therapeutic target for ovarian cancer.