FBXO28 promotes proliferation, invasion, and metastasis of pancreatic cancer cells through regulation of SMARCC2 ubiquitination.
FBXO28 promotes proliferation, invasion, and metastasis of pancreatic cancer cells through regulation of SMARCC2 ubiquitination.
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DOI：
10.18632/aging.204780
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发表时间：
2023-06-21
期刊：
影响因子：
5.2
通讯作者：
Pan, Yaozhen
中科院分区：
文献类型：
--
作者：
Liu, Songbai;Liu, Peng;Zhu, Changhao;Yang, Rui;He, Zhiwei;Li, Yongning;Li, Ying;Fei, Xiaobin;Hou, Junyi;Wang, Xing;Pan, Yaozhen
E3 连接酶 F-box 唯一蛋白 28 (FBXO28) 属于 F-box 蛋白家族，在肿瘤发展中发挥着关键作用。然而，FBXO28在胰腺癌（PC）中的潜在功能及其分子机制仍不清楚。在本研究中，我们检测了PC中FBXO28的表达及其生物学作用，并探讨了FBXO28介导的PC细胞增殖、侵袭和转移的机制。与癌旁组织和人正常胰腺导管上皮细胞相比，FBXO28在PC组织和细胞系中高表达。 FBXO28的高表达与PC患者的生存预后呈负相关。功能测定表明，FBXO28 在体外和体内促进 PC 细胞增殖、侵袭和转移。此外，使用免疫沉淀-质谱法鉴定SMARCC2为FBXO28的靶标； SMARCC2的上调可以逆转FBXO28过表达促进PC细胞增殖、侵袭和转移的作用。从机制上讲，FBXO28 通过增加 SMARCC2 泛素化和蛋白质降解来抑制翻译后 SMARCC2 表达。总之，FBXO28 在 PC 中具有潜在作用，可能通过 SMARCC2 泛素化促进 PC 进展。因此，FBXO28可能是PC的潜在治疗靶点。
The E3 ligase F-box only protein 28 (FBXO28) belongs to the F-box family of proteins that play a critical role in tumor development. However, the potential function of FBXO28 in pancreatic cancer (PC) and its molecular mechanism remain unclear. In this study, we examined FBXO28 expression in PC and its biological role and explored the mechanism of FBXO28-mediated proliferation, invasion, and metastasis of PC cells. Compared with paracancerous tissues and human normal pancreatic ductal epithelial cells, FBXO28 was highly expressed in PC tissues and cell lines. High expression of FBXO28 was negatively correlated with the survival prognosis of patients with PC. Functional assays indicated that FBXO28 promoted PC cell proliferation, invasion, and metastasis in vitro and in vivo. Furthermore, immunoprecipitation-mass spectrometry was used to identify SMARCC2 as the target of FBXO28; upregulation of SMARCC2 can reverse the effect of overexpression of FBXO28 on promoting the proliferation, invasion, and metastasis of PC cells. Mechanistically, FBXO28 inhibited SMARCC2 expression in post-translation by increasing SMARCC2 ubiquitination and protein degradation. In conclusion, FBXO28 has a potential role in PC, possibly promoting PC progression through SMARCC2 ubiquitination. Thus, FBXO28 might be a potential treatment target in PC.
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