靶向SOAT1对前列腺癌的作用和机制研究

doi:10.3877/cma.j.issn.1674-3253.2026.01.014

目的

探讨SOAT1基因表达在前列腺癌发生发展中的作用及机制。

方法

分别使用TCGA临床数据集、前列腺癌细胞系分析和验证SOAT1基因的表达情况。基因表达、甲基化水平和生存分析了解SOAT1基因表达与前列腺癌患者预后的相关性。CRISPR-Cas9技术建立基因敲除细胞株，蛋白免疫印迹检验基因表达水平，MTS、克隆形成实验和Transwell等分析细胞增殖和迁移的能力。荧光定量聚合酶链反应、蛋白免疫印迹、高分辨质谱和细胞能量代谢等分析SOAT1基因在前列腺癌细胞中的作用和分子机制。

结果

SOAT1在前列腺癌组织中表达升高（P<0.05），高表达SOAT1基因的患者生存率下降。SOAT1表达不受雄激素受体信号通路调控，与获得性去势抵抗的过程无关（P>0.05）。敲除SOAT1基因通过减少线粒体代谢（氧耗呼吸值下降约45%，三磷酸腺苷生成减少约55%）抑制前列腺癌细胞的增殖，并不依赖雄激素代谢途径。

结论

靶向敲除SOAT1可以通过降低线粒体代谢抑制前列腺癌细胞增殖、上皮-间质转化和肿瘤干性，能够作为潜在的治疗靶点。

关键词: 前列腺癌, SOAT1, 基因敲除, 线粒体代谢, 细胞增殖

Objective

To investigate the role and mechanisms of SOAT1 gene expression in the development and progression of prostate cancer.

Methods

The expression of the SOAT1 gene was analyzed based on TCGA datasets and validated in prostate cancer cell lines. The correlation between SOAT1 gene expression and patient prognosis in prostate cancer was assessed through gene expression, methylation levels, and survival analysis. A gene knockout cell line was established using CRISPR-Cas9 technology, and gene expression levels were verified by Western blot. Cell proliferation and migration abilities were analyzed using MTS, colony formation, and transwell assays. The role and molecular mechanisms of SOAT1 in prostate cancer cells were further investigated through quantitative real-time polymerase chain reaction, Western blot, high-resolution mass spectrometry, and cellular energy metabolism experiments.

Results

SOAT1 expression was upregulated in prostate cancer tissues (P<0.05), and high SOAT1 expression was associated with decreased patient survival. SOAT1 expression was not regulated by the androgen receptor signaling pathway and was unrelated to the process of acquired castration resistance (P>0.05). Knockout of SOAT1 inhibited prostate cancer cell proliferation by reducing mitochondrial metabolism (approximately 45% decrease in oxygen consumption and 55% reduction in production of adenosine triphosphate), independent of the androgen metabolic pathway.

Conclusion

Targeted knockout of SOAT1 can inhibit prostate cancer cell proliferation, epithelial-mesenchymal transition (EMT), and tumor stemness by reducing mitochondrial metabolism, suggesting its potential as a therapeutic target.

Key words: Prostate cancer, SOAT1, Gene knockout, Mitochondrial metabolism, Cell proliferation

图1 PCa和正常前列腺组织SOAT1基因表达情况及与预后的关系注：a为通过UALCAN在线平台分析TCGA-PRAD数据集中SOAT1基因在前列腺癌（PCa）组织中的表达；b为PCa组织中SOAT1甲基化水平降低；c示高表达SOAT1 PCa患者生存率下降但不显著；*示P<0.05

图2 PCa细胞中SOAT1基因表达与雄激素信号途径的关系注：a为基因SOAT1在前列腺癌细胞和正常前列腺上皮细胞（PWR-1E）中的mRNA相对表达水平分析；b为基因SOAT1在前列腺癌细胞和正常前列腺上皮细胞（RWPE-1）中的蛋白表达水平；c为荧光定量PCR实验分析雄激素依赖PCa细胞系（LNCaP）和非雄激素依赖PCa细胞系（C4、C4-2、C4-2B）中SOAT1的表达；d为蛋白免疫印迹实验检测SOAT1的表达水平；ns为差异无统计学意义（P>0.05）

图3 敲除SOAT1对PCa细胞增殖的影响注：a为蛋白免疫印迹实验验证SOAT1基因敲除；b为细胞增殖实验分析SOAT1敲除对PCa细胞的影响；c为克隆形成实验检测敲除SOAT1对PCa细胞的抑制作用；d为柱状图统计分析克隆数量；22RV1和PC3为PCa细胞系；^***示P<0.001

图4 靶向SOAT1对PCa细胞上皮-间质转化和肿瘤干性的影响注：a为transwell实验分析敲除SOAT1基因抑制PCa细胞的迁移能力；b为柱状图统计分析SOAT1敲除对PCa细胞迁移的影响；c为荧光定量PCR实验检测敲除SOAT1对PCa细胞肿瘤干性相关标记物的影响；d为蛋白免疫印迹实验检测SOAT1敲除细胞的上皮-间质转化相关标记物变化；^***示P<0.001

图5 敲除SOAT1抑制PCa细胞增殖的机制注：a为胆固醇从头合成和雄激素生成途径示意图；b为细胞增殖实验分析二氢睾酮、醋酸阿比特龙和恩扎鲁胺对SOAT1敲除PCa细胞增殖能力的影响；c为高分辨质谱检测胆固醇合成途径相应代谢物（IPP、FPP、CoQ10）等的含量变化；d为能量代谢分析显示CoQ10对SOAT1敲除PCa细胞线粒体氧耗量的影响；e为柱状图统计CoQ10对SOAT1敲除PCa细胞线粒体基础呼吸和三磷酸腺苷生成能力的影响；f为细胞增殖实验分析CoQ10对SOAT1敲除PCa细胞增殖的影响；FPP为法尼基焦磷酸，IPP为异戊烯基二磷酸，CoQ10为辅酶Q10；^*示P<0.05，^**示P<0.01，^***示P<0.001

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The role and mechanisms of targeting SOAT1 in prostate cancer

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The role and mechanisms of targeting SOAT1 in prostate cancer