Xie Jianbing, Chen Qiren, Li Lixian, Liu Jinyu
Department of Urology, Affiliated Hospital of Putian University, Putian, Fujian, China.
Department of Breast Surgery, Affiliated Hospital of Putian University, Putian, Fujian, China.
Braz J Med Biol Res. 2025 May 9;58:e14445. doi: 10.1590/1414-431X2025e14445. eCollection 2025.
The primary objective of the present study was to identify differentially expressed genes (DEGs) associated with castration-resistant prostate cancer (CRPC) to verify the potential mechanism of CRPC progression. DEGs from CRPC datasets were filtered with a P<0.05 and Spearman correlation coefficient ≥0.3. Serpin peptidase inhibitor, clade A member 3 (SERPINA3), was uniquely present in three CRPC datasets, and its low expression in CRPC was confirmed in cell lines and tissues. Colony formation, transwell assays, and subcutaneous tumor formation experiments in mice demonstrated that overexpression of SERPINA3 may significantly inhibit the proliferation and invasion of PC3 cells. Mechanistic studies revealed that, in prostate cancer (PCa), SERPINA3 can activate the interleukin (IL)-17 and tumor necrosis factor (TNF)α signaling pathways by promoting the expression of CXC chemokine ligand 2 (CXCL2), thereby increasing the recruitment of M1 macrophages into the tumor microenvironment and inhibiting the progression of PCa. The current results indicated that the expression of SERPINA3 may be negatively correlated with CRPC, and it could promote the M1 polarization of macrophages and inhibit the progression of CRPC by increasing the expression of CXCL2.
本研究的主要目的是鉴定与去势抵抗性前列腺癌（CRPC）相关的差异表达基因（DEG），以验证CRPC进展的潜在机制。来自CRPC数据集的DEG通过P<0.05和Spearman相关系数≥0.3进行筛选。丝氨酸蛋白酶抑制剂A3家族成员（SERPINA3）在三个CRPC数据集中独特存在，并且在细胞系和组织中证实其在CRPC中低表达。小鼠的集落形成、Transwell实验和皮下肿瘤形成实验表明，SERPINA3的过表达可能显著抑制PC3细胞的增殖和侵袭。机制研究显示，在前列腺癌（PCa）中，SERPINA3可通过促进CXC趋化因子配体2（CXCL2）的表达来激活白细胞介素（IL）-17和肿瘤坏死因子（TNF）α信号通路，从而增加M1巨噬细胞向肿瘤微环境的募集并抑制PCa的进展。目前的结果表明，SERPINA3的表达可能与CRPC呈负相关，并且它可以通过增加CXCL2的表达促进巨噬细胞的M1极化并抑制CRPC的进展。
