Astragalus Polysaccharides Inhibits Tumorigenesis and Lipid Metabolism Through miR-138-5p/SIRT1/SREBP1 Pathway in Prostate Cancer
Astragalus Polysaccharides Inhibits Tumorigenesis and Lipid Metabolism Through miR-138-5p/SIRT1/SREBP1 Pathway in Prostate Cancer
复制标题
黄芪多糖通过 miR-138-5p/SIRT1/SREBP1 通路抑制前列腺癌肿瘤发生和脂质代谢
DOI：
10.3389/fphar.2020.00598
复制
发表时间：
2020-05-05
影响因子：
5.6
通讯作者：
Jia, Yingjie
中科院分区：
文献类型：
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作者：
Guo, Shanqi;Ma, Baojie;Jia, Yingjie
黄芪多糖（APS）是一种传统的中药，已被证实参与多种生物学过程，包括炎症、代谢和致癌作用。然而，APS对前列腺癌（PCa）的具体机制仍不清楚。本研究发现，APS在体内外均能显著抑制PCa细胞的增殖和侵袭，且呈剂量依赖和时间依赖关系。此外，细胞甘油三酯和胆固醇水平也显着降低APS治疗。微阵列数据显示，SIRT 1的表达显着抑制下APS曝光。机制研究表明，SIRT 1的过表达通过激活AMPK磷酸化抑制脂质代谢，从而抑制SREBP 1的表达和核转位。另外，SIRT 1的敲低显著促进AMPK/SREBP 1信号传导及其相关靶基因。此外，我们还发现miR-138- 5 p通过靶向SIRT 1的3′UTR区域，显著抑制SIRT 1的表达，从而调节细胞代谢。总之，我们的研究结果表明，APS通过miR-138- 5 p/SIRT 1/SREBP 1途径抑制PCa的肿瘤发生和脂质代谢。
Astragalus polysaccharides (APS) is a traditional Chinese medicine and have been proved to involve in multiple biological processes, including inflammation, metabolism, and carcinogenics. However, the specific mechanisms by which APS on prostate cancer (PCa) remains largely unknown. In the current study, we found APS greatly inhibited the proliferation and invasion of PCa cells in a dose-dependent and time-dependent manner in vitro and in vivo. In addition, cellular triglyceride and cholesterol levels were also decreased significantly under APS treatment. Microarray data revealed the SIRT1 expression was markably suppressed under APS exposure. Mechanistic studies demonstrated that over-expression of SIRT1 inhibits the expression and nuclear translocation of SREBP1 via activating AMPK phosphorylation to suppress lipid metabolism. Otherwise, knockdown of SIRT1 significantly promotes AMPK/SREBP1 signaling and its associated target genes. Besides, we also found miR-138-5p was greatly inhibited the SIRT1 expression to regulating cell metabolism by targeting its 3′UTR region. To summarize, our findings suggested that APS inhibits tumorigenesis and lipid metabolism through miR-138-5p/SIRT1/SREBP1 pathways in PCa.