Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China; Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Toxicol Lett. 2021 Sep 15;348:50-58. doi: 10.1016/j.toxlet.2021.05.006. Epub 2021 May 28.
Antimony is a common environmental contaminant that causes biological toxicity in exposed populations worldwide. Previous studies have revealed that antimony promotes prostate cancer growth by stabilizing the c-Myc protein and mimicking androgen activity. However, the role of lncRNAs in the regulation of antimony-induced carcinogenesis remains unknown, and the precise mechanisms need to be explored. In the present study, we found that chronic exposure to antimony promoted cell growth and lipid metabolic disequilibrium in prostate cancer. Mechanistically, we identified a long noncoding RNA molecule, PCA3, that was substantially upregulated in LNCaP cells in response to long-term antimony exposure. Functional studies indicated that abnormal PCA3 expression modulated antimony-induced proliferation and cellular triglyceride and cholesterol levels. In addition, PCA3 levels were found to be inversely correlated with MIR-132-3 P levels by acting as a decoy for MIR-132-3P. Besides, SREBP1 directly interacted with MIR-132-3 P to increase cell growth and disrupt lipid metabolism by targeting its 3'UTR regions. Taken together, our results revealed that lncRNA PCA3 promotes antimony-induced lipid metabolic disorder in prostate cancer by targeting MIR-132-3 P/SREBP1 signaling.
锑是一种常见的环境污染物，会对全球暴露人群造成生物毒性。先前的研究表明，锑通过稳定 c-Myc 蛋白并模拟雄激素活性来促进前列腺癌的生长。然而，lncRNAs 在调节锑诱导的致癌作用中的作用尚不清楚，需要进一步探讨其确切的机制。在本研究中，我们发现慢性暴露于锑会促进前列腺癌细胞生长和脂质代谢失衡。在机制上，我们鉴定了一种长非编码 RNA 分子 PCA3，它在 LNCaP 细胞中对长期锑暴露有明显的上调。功能研究表明，异常的 PCA3 表达通过充当 MIR-132-3P 的诱饵来调节锑诱导的增殖和细胞内三酰甘油和胆固醇水平。此外，PCA3 水平通过与 MIR-132-3P 相互作用，作为 MIR-132-3P 的诱饵，与 MIR-132-3P 的水平呈负相关。此外，SREBP1 通过靶向其 3'UTR 区域与 MIR-132-3P 直接相互作用，增加细胞生长并破坏脂质代谢。综上所述，我们的研究结果表明，lncRNA PCA3 通过靶向 MIR-132-3P/SREBP1 信号通路促进前列腺癌细胞中锑诱导的脂质代谢紊乱。
