PDF(Pubmed)
Abstract：
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.
摘要：
E3连接酶仅F-box蛋白28(FBXO28)属于在肿瘤发展中起关键作用的F-box蛋白家族。然而,FBXO28在胰腺癌（PC）中的潜在功能及其分子机制尚不清楚。在这项研究中,我们研究了FBXO28在PC中的表达及其生物学作用，并探讨了FBXO28介导的增殖机制，入侵,和PC细胞的转移。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。功能试验表明FBXO28促进PC细胞增殖,入侵,和体内外转移。此外，免疫共沉淀-质谱鉴定SMARCC2为FBXO28的靶标；上调SMARCC2可以逆转FBXO28过表达的促增殖作用，入侵,和PC细胞的转移。机械上,FBXO28通过增加SMARCC2泛素化和蛋白质降解抑制翻译后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的潜在治疗靶标。
