首页|SYVN1介导FASN泛素化降解促进骨肉瘤细胞失巢凋亡

SYVN1介导FASN泛素化降解促进骨肉瘤细胞失巢凋亡

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目的 探讨FASN在骨肉瘤远处转移过程中受调控的机制.方法 应用骨肉瘤失巢凋亡抵抗模型,通过在线预测、蛋白组学测序以及CO-IP实验等,筛选出与FASN相互作用的E3 连接酶;Western blot、泛素化实验检测FASN蛋白的泛素化水平;应用流式细胞术,肿瘤成球实验、裸鼠原位骨肉瘤肺转移模型等,探讨FASN泛素化在骨肉瘤远处转移中的调控机制.结果 FASN在失巢凋亡抵抗细胞中泛素化水平降低而表达升高,预测结果提示SYVN1 是FASN泛素化的E3 连接酶;过表达SYVN1 可以诱导骨肉瘤细胞失巢凋亡,并降低骨肉瘤原位成瘤和远处转移能力.结论 E3连接酶SYVN1 在骨肉瘤失巢凋亡抵抗过程中降低,导致FASN泛素化下降而表达升高,过表达SYVN1 可抑制骨肉瘤进程.
SYVN1-mediated FASN Ubiquitination Promotes Osteosarcoma Cells Anoikis
Objective To explore the mechanism that regulated FASN during distant metastasis of osteosarcoma.Meth-ods Based on the anoikis resistance model of osteosarcoma,online prediction,proteomic sequencing,and CO-IP experiments were used to screened the E3 ligase interacting with FASN;Western blot and ubiquitination experiments were used to detect the ubiquitination level of FASN proteins;and we applied flow cytometry,tumor spheroid formation experiments,and the in situ osteo-sarcoma lung metastasis model of nude mice to explore the regulation mechanism of FASN ubiquitination in the distant metastasis of osteosarcoma.ubiquitination in distant metastasis of osteosarcoma.Results The ubiquitination level of FASN was decreased while its expression was increased in loss-of-nest apoptosis-resistant cells,and the predicted results suggested that SYVN1 was an E3 ligase for FASN ubiquitination;overexpression of SYVN1 induced loss-of-nest apoptosis of osteosarcoma cells and decreased the ability of osteosarcoma to form tumors and metastasize remotely in situ.Conclusion The E3 ligase SYVN1 was reduced in the process of resistance to loss-of-nest apoptosis in osteosarcoma,resulting in decreased ubiquitination and increased expression of FASN,and overexpression of SYVN1 inhibited osteosarcoma progression.

OsteosarcomaFASNSYVN1UbiquitinationDistant metastasis

钟南山、杨枫、刘志礼

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330006 南昌大学第一附属医院

330006 南昌大学脊柱脊髓研究所

骨肉瘤 FASN SYVN1 泛素化 远处转移

江西省自然科学基金面上项目

20202BAB206044

2024

实用癌症杂志
江西省肿瘤医院 江西省肿瘤研究所

实用癌症杂志

影响因子:1.241
ISSN:1001-5930
年,卷(期):2024.39(3)
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