{"title":"TRIM47 通过 FBP1 和 FOXO1 促进前列腺癌的沃伯格效应并降低铁变态反应。","authors":"Chubiao Zhao, Zengqin Liu, Junming Peng, Jiansheng Huang, Jinan Guo","doi":"10.21037/tau-23-605","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PC), a malignant tumor occurring in the male prostate tissue, has a high incidence rate. In this study, we explored the role of tripartite motif 47 (TRIM47) in the progression of PC and its underlying mechanism.</p><p><strong>Methods: </strong>PC and paracancerous tissues were collected from Shenzhen Peoples's Hospital. The following methods were employed in this experiment: quantitative polymerase chain reaction (qPCR), immunofluorescent staining, cell counting kit-8 (CCK-8), ethynyl deoxyuridine (EdU), and Western blot.</p><p><strong>Results: </strong>The expression levels of TRIM47 were up-regulated in patients with PC. TRIM47 was found to promote cell growth and induce the Warburg effect, while also reducing ferroptosis in PC cells. Conversely, the knockdown of TRIM47 [small interfering RNA, (si)-TRIM47] decreased cell growth and the Warburg effect, while promoting ferroptosis in PC cells. Additionally, TRIM47 was observed to induce the protein expression levels of fructose-1,6-bisphosphatase 1 (FBP1) and forkhead box protein O1 (FOXO1) in PC cells. Further, TRIM47 protein was found to interact with both the FBP1 and FOXO1 proteins in the PC cells. The inhibition of FBP1 attenuated the effects of TRIM47 on the Warburg effect in PC cells, while the inhibition of FOXO1 diminished the effects of TRIM47 on ferroptosis in PC cells.</p><p><strong>Conclusions: </strong>Our findings suggest that TRIM47 promotes the Warburg effect of PC by inducing FBP1 and FOXO1. 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Further, TRIM47 protein was found to interact with both the FBP1 and FOXO1 proteins in the PC cells. The inhibition of FBP1 attenuated the effects of TRIM47 on the Warburg effect in PC cells, while the inhibition of FOXO1 diminished the effects of TRIM47 on ferroptosis in PC cells.</p><p><strong>Conclusions: </strong>Our findings suggest that TRIM47 promotes the Warburg effect of PC by inducing FBP1 and FOXO1. 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引用次数: 0
摘要
背景：前列腺癌（PC）是一种发生在男性前列腺组织中的恶性肿瘤，发病率很高。本研究探讨了三方基序 47（TRIM47）在前列腺癌进展过程中的作用及其内在机制：方法：PC和癌旁组织取自深圳市人民医院。本实验采用了以下方法：定量聚合酶链反应（qPCR）、免疫荧光染色、细胞计数试剂盒-8（CCK-8）、乙炔基脱氧尿苷（EdU）、Western blot：结果：TRIM47在PC患者中的表达水平呈上调趋势。结果表明：TRIM47在PC患者中的表达水平上调，TRIM47能促进细胞生长并诱导沃伯格效应，同时还能降低PC细胞的铁突变。相反，敲除 TRIM47 [small interfering RNA, (si)-TRIM47]会降低 PC 细胞的生长和沃伯格效应，同时促进铁凋亡。此外，还观察到 TRIM47 能诱导 PC 细胞中果糖-1,6-二磷酸酶 1（FBP1）和叉头盒蛋白 O1（FOXO1）的蛋白表达水平。此外，还发现 TRIM47 蛋白与 PC 细胞中的 FBP1 和 FOXO1 蛋白相互作用。抑制FBP1可减轻TRIM47对PC细胞沃伯格效应的影响，而抑制FOXO1则可减弱TRIM47对PC细胞铁变态反应的影响：我们的研究结果表明，TRIM47通过诱导FBP1和FOXO1促进PC的沃伯格效应。因此，我们的研究结果表明，靶向 TRIM47 可作为治疗 PC 的一种可行的治疗策略。
TRIM47 promotes the Warburg effect and reduces ferroptosis in prostate cancer by FBP1 and FOXO1.
Background: Prostate cancer (PC), a malignant tumor occurring in the male prostate tissue, has a high incidence rate. In this study, we explored the role of tripartite motif 47 (TRIM47) in the progression of PC and its underlying mechanism.
Methods: PC and paracancerous tissues were collected from Shenzhen Peoples's Hospital. The following methods were employed in this experiment: quantitative polymerase chain reaction (qPCR), immunofluorescent staining, cell counting kit-8 (CCK-8), ethynyl deoxyuridine (EdU), and Western blot.
Results: The expression levels of TRIM47 were up-regulated in patients with PC. TRIM47 was found to promote cell growth and induce the Warburg effect, while also reducing ferroptosis in PC cells. Conversely, the knockdown of TRIM47 [small interfering RNA, (si)-TRIM47] decreased cell growth and the Warburg effect, while promoting ferroptosis in PC cells. Additionally, TRIM47 was observed to induce the protein expression levels of fructose-1,6-bisphosphatase 1 (FBP1) and forkhead box protein O1 (FOXO1) in PC cells. Further, TRIM47 protein was found to interact with both the FBP1 and FOXO1 proteins in the PC cells. The inhibition of FBP1 attenuated the effects of TRIM47 on the Warburg effect in PC cells, while the inhibition of FOXO1 diminished the effects of TRIM47 on ferroptosis in PC cells.
Conclusions: Our findings suggest that TRIM47 promotes the Warburg effect of PC by inducing FBP1 and FOXO1. Thus, our findings suggest that targeting TRIM47 could serve as a viable therapeutic strategy for the treatment of PC.
期刊介绍：
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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