The glycoprotein mucin-1 negatively regulates GalNAc transferase 5 expression in pancreatic cancer
The glycoprotein mucin-1 negatively regulates GalNAc transferase 5 expression in pancreatic cancer
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DOI：
10.1002/1873-3468.13532
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发表时间：
2019-07-21
期刊：
影响因子：
3.5
通讯作者：
Radhakrishnan, Prakash
中科院分区：
文献类型：
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作者：
Caffrey, Thomas;Sagar, Satish;Radhakrishnan, Prakash
糖蛋白粘蛋白-1（MUC 1）的异常表达与胰腺癌的进展和转移有关，其介导靶基因的致癌转录调控。在本研究中，我们证明了MUC 1下调胰腺癌中肿瘤抑制多肽N-乙酰氨基半乳糖转移酶5的表达。ChIP芯片分析显示MUC 1胞质尾区与GALNT 5基因中的调控元件结合。此外，MUC 1增加p53和c-Jun的结合，并减少Sp1与GALNT 5的近端启动子和外显子区域的结合。我们还观察到，在人胰腺癌中，N-乙酰氨基半乳糖转移酶5的表达与MUC 1的表达成反比。这些结果表明，MUC 1下调N-乙酰氨基半乳糖转移酶5在胰腺癌中的表达，通过其胞质结构域修改的转录因子的启动子占用。
Aberrant expression of the glycoprotein mucin-1 (MUC1) has been associated with pancreatic cancer progression and metastasis as a result of mediating the oncogenic transcriptional regulation of target genes. In the present study, we demonstrate that MUC1 downregulates the expression of the tumor suppressor polypeptide N-acetylgalactosaminyltransferase 5 in pancreatic cancer. ChIP-on-chip analysis revealed that the MUC1 cytoplasmic tail binds to regulatory elements in the GALNT5 gene. Additionally, MUC1 increases binding of p53 and c-Jun and decreases the binding of Sp1 to the proximal promoter and exonic regions of GALNT5. We also observed that expression of N-acetylgalactosaminyltransferase 5 is inversionally proportional to MUC1 expression in human pancreatic cancer. These results demonstrate that MUC1 downregulates the expression of N-acetylgalactosaminyltransferase 5 in pancreatic cancer by modifying the promoter occupancy of transcription factors through its cytoplasmic domain.