Zhu Shuaizhi, Kou Zengshun, Xiao Chengcheng, Wang Lu, Zhu Jiaxi, Zheng Yu, Zhu Hai
Department of Urology, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province, China.
Department of Urology, Qingdao West Coast New Area District Hospital, Qingdao, Shandong Province, China.
Sci Rep. 2025 Jun 6;15(1):19886. doi: 10.1038/s41598-025-04717-7.
Emerging evidence from recent studies demonstrates that the FGL1/LAG-3 interaction axis plays a crucial role in mediating tumor immune evasion mechanisms, particularly through the suppression of T lymphocyte effector functions. However, the role of FGL1 in prostate cancer (PCa) remains unclear. Data was downloaded from The Cancer Genome Atlas (TCGA) database, and subjected to differential expression analysis. Single gene differential analysis to determine the correlation between FGL1 and DNAJC12 expression levels in prostate cancer. The expression of FGL1 was silenced by siRNA in PC3 prostate cancer cells. Lentiviruses infected DU145 to overexpress FGL1. Cell proliferation, apoptosis and EMT-related markers were detected in vitro. Animal experiments further confirmed the effect of FGL1 on prostate cancer. Up-regulated gene FGL1 was identified as the selected gene in this study among 3011 Differentially expressed genes. FGL1 had the highest positive relation with DNAJC12. The OS of PCa patients with high expression of FGL1 was significantly shorter. After silencing FGL1, PC3 cell proliferation was inhibited by 0.58-fold, while apoptosis increased by 16%, and the expression of cleaved-caspase-3 increased, while the expression of DNAJC12 and BCL-2 decreased. After overexpression of FGL1, the number of DU145 cells increased by 2.05-fold, the expression of cleaved-caspase-3 was inhibited, E-cadherin expression decreased, while N-cadherin and Vimentin expression increased. Tumor growth was inhibited, and the expression of FN1, n-cadherin, Vimentin and β-catenin decreased, while the expression of E-cadherin increased after silencing FGL1. Silencing FGL1 promotes prostate cancer cell apoptosis and inhibits EMT progression. FGL1 may be an independent prognostic marker and therapeutic target in PCa.
近期研究的新证据表明，FGL1/LAG-3相互作用轴在介导肿瘤免疫逃逸机制中起关键作用，尤其是通过抑制T淋巴细胞效应功能。然而，FGL1在前列腺癌（PCa）中的作用仍不清楚。从癌症基因组图谱（TCGA）数据库下载数据，并进行差异表达分析。通过单基因差异分析确定前列腺癌中FGL1与DNAJC12表达水平之间的相关性。在PC3前列腺癌细胞中，FGL1的表达通过小干扰RNA（siRNA）沉默。慢病毒感染DU145以过表达FGL1。体外检测细胞增殖、凋亡和上皮-间质转化（EMT）相关标志物。动物实验进一步证实了FGL1对前列腺癌的影响。在3011个差异表达基因中，上调基因FGL1被确定为本研究中的选定基因。FGL1与DNAJC12的正相关性最高。FGL1高表达的PCa患者的总生存期显著缩短。沉默FGL1后，PC3细胞增殖受到0.58倍的抑制，而凋亡增加了16%，裂解的半胱天冬酶-3表达增加，而DNAJC12和BCL-2的表达下降。过表达FGL1后，DU145细胞数量增加了2.05倍，裂解的半胱天冬酶-3表达受到抑制，E-钙黏蛋白表达下降，而N-钙黏蛋白和波形蛋白表达增加。沉默FGL1后，肿瘤生长受到抑制，纤连蛋白1、N-钙黏蛋白、波形蛋白和β-连环蛋白的表达下降，而E-钙黏蛋白的表达增加。沉默FGL1可促进前列腺癌细胞凋亡并抑制EMT进程。FGL1可能是PCa的独立预后标志物和治疗靶点。
