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TRIM47通过FBP1和FOXO1促进前列腺癌的瓦伯格效应并减少铁死亡。

TRIM47 promotes the Warburg effect and reduces ferroptosis in prostate cancer by FBP1 and FOXO1.

作者信息

Zhao Chubiao, Liu Zengqin, Peng Junming, Huang Jiansheng, Guo Jinan

机构信息

Department of Urology, Shenzhen People's Hospital, Shenzhen, China.

出版信息

Transl Androl Urol. 2024 Sep 30;13(9):1991-2004. doi: 10.21037/tau-23-605. Epub 2024 Sep 26.

DOI:10.21037/tau-23-605
PMID:39434735
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11491198/
Abstract

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.

摘要

背景

前列腺癌（PC）是发生于男性前列腺组织的恶性肿瘤，发病率较高。在本研究中，我们探讨了三联基序蛋白47（TRIM47）在前列腺癌进展中的作用及其潜在机制。

方法

从深圳市人民医院收集前列腺癌组织及癌旁组织。本实验采用以下方法：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）和蛋白质免疫印迹法。

结果

前列腺癌患者中TRIM47的表达水平上调。发现TRIM47可促进细胞生长并诱导瓦伯格效应，同时还可减少前列腺癌细胞中的铁死亡。相反，敲低TRIM47 [小干扰RNA，（si）-TRIM47]可降低细胞生长和瓦伯格效应，同时促进前列腺癌细胞中的铁死亡。此外，观察到TRIM47可诱导前列腺癌细胞中果糖-1,6-二磷酸酶1（FBP1）和叉头框蛋白O1（FOXO1）的蛋白表达水平。此外，发现TRIM47蛋白在前列腺癌细胞中与FBP1和FOXO1蛋白均相互作用。抑制FBP1可减弱TRIM47对前列腺癌细胞瓦伯格效应的影响，而抑制FOXO1可减弱TRIM47对前列腺癌细胞铁死亡的影响。

结论

我们的研究结果表明，TRIM47通过诱导FBP1和FOXO1促进前列腺癌的瓦伯格效应。因此，我们的研究结果表明，靶向TRIM47可能是治疗前列腺癌的一种可行治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/70dbea871ed8/tau-13-09-1991-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/2baa0756d892/tau-13-09-1991-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/fdb30e698b88/tau-13-09-1991-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/26ae5fdd21e1/tau-13-09-1991-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/bb86aef9711e/tau-13-09-1991-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/62f7cfaa5d2f/tau-13-09-1991-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/4011a0f94c7c/tau-13-09-1991-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/3256d4c8cf55/tau-13-09-1991-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/70dbea871ed8/tau-13-09-1991-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/2baa0756d892/tau-13-09-1991-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/fdb30e698b88/tau-13-09-1991-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/26ae5fdd21e1/tau-13-09-1991-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/bb86aef9711e/tau-13-09-1991-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/62f7cfaa5d2f/tau-13-09-1991-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/4011a0f94c7c/tau-13-09-1991-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/3256d4c8cf55/tau-13-09-1991-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/11491198/70dbea871ed8/tau-13-09-1991-f8.jpg

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