Abstract：
Microcystin-leucine-arginine (MC-LR) is positively linked with multiple cancers in humans. However, the association between MC-LR and the risk and prognosis of prostate cancer has not been conducted in epidemiological studies. No reported studies have linked MC-LR exposure to the poor prognosis of prostate cancer by conducting experimental studies. The content of MC-LR was detected in most of the aquatic food in wet markets and supermarkets in Nanjing and posed a health risk for consumers. MC-LR levels in both prostate cancer tissues and serum were significantly higher than controls. The adjusted odds ratio (OR) for prostate cancer risk by serum MC-LR was 1.75 (95%CI: 1.21-2.52) in the whole subjects, and a positive correlation between MC-LR and advanced tumor stage was observed. Survival curve analysis indicated patients with higher MC-LR levels in tissues exhibited poorer overall survival. Human, animal, and cell studies confirmed that MC-LR exposure increases the expression of estrogen receptor-α (ERα) and promotes epithelial-mesenchymal transition (EMT) in prostate cancer. Moreover, MC-LR-induced decreased E-cadherin levels, increased vimentin levels, and increased migratory and invasive capacities of prostate cancer cells were markedly suppressed upon ERα knockdown. MC-LR-induced xenograft tumor growth and lung metastasis in BALB/c nude mice can be effectively alleviated with ERα knockdown. Our data demonstrated that MC-LR upregulated vimentin and downregulated E-cadherin through activating ERα, promoting migration and invasion of prostate cancer cells. Our findings highlight the role of MC-LR in prostate cancer, providing new perspectives to understand MC-LR-induced prostatic toxicity.
摘要：
微囊藻毒素-亮氨酸-精氨酸（MC-LR）与人类多种癌症呈正相关。然而,MC-LR与前列腺癌风险和预后之间的关联尚未在流行病学研究中进行.没有报道的研究通过进行实验研究将MC-LR暴露与前列腺癌的不良预后联系起来。在南京的超市和超市中，大多数水产食品中都检测到MC-LR的含量，对消费者构成健康风险。前列腺癌组织和血清中的MC-LR水平均明显高于对照组。在整个受试者中，通过血清MC-LR对前列腺癌风险的校正比值比（OR）为1.75（95CI：1.21-2.52），MC-LR与晚期肿瘤分期呈正相关。生存曲线分析表明，组织中MC-LR水平较高的患者总生存期较差。人类,动物,细胞研究证实MC-LR暴露可增加前列腺癌中雌激素受体-α（ERα）的表达并促进上皮-间质转化（EMT）。此外，MC-LR诱导的E-钙粘蛋白水平降低，增加波形蛋白水平，ERα敲低后，前列腺癌细胞的迁移和侵袭能力的增加被显著抑制。ERα敲低可有效缓解MC-LR诱导的BALB/c裸鼠移植瘤生长和肺转移。我们的数据表明，MC-LR通过激活ERα上调波形蛋白和下调E-cadherin，促进前列腺癌细胞的迁移和侵袭。我们的发现强调了MC-LR在前列腺癌中的作用，为了解MC-LR诱导的前列腺毒性提供了新的视角。
