DNA methylation directly downregulates human cathelicidin antimicrobial peptide gene (CAMP) promoter activity.
DNA methylation directly downregulates human cathelicidin antimicrobial peptide gene (CAMP) promoter activity.
复制标题
DNA甲基化直接下调人导管素抗菌肽基因（CAMP）启动子活性
DOI：
10.18632/oncotarget.15847
复制
发表时间：
2017-04-25
期刊：
影响因子：
--
通讯作者：
Zou X
中科院分区：
文献类型：
--
作者：
Chen X;Qi G;Qin M;Zou Y;Zhong K;Tang Y;Guo Y;Jiang X;Liang L;Zou X
LL-37是人抗菌肽CAMP的活性产物，具有广谱抗菌活性。LL-37还在免疫调节、血管生成和调节细胞凋亡中具有重要的生理功能。LL-37在口腔鳞状细胞癌（OSCC）中的作用尚不清楚。DNA甲基化和人CAMP表达之间的相关性也是未知的。在此，通过免疫组织化学评估正常和OSCC组织中的人CAMP/LL-37表达。结果表明，CAMP/LL-37的低表达与肿瘤的分化程度、淋巴结转移有关，并促进肿瘤的进展。检测到人CAMP启动子区的细胞特异性甲基化模式。用DNA去甲基化试剂5-氮杂-2 ′-脱氧胞苷处理可以增加上皮癌细胞中人CAMP的表达。报告基因分析显示，未甲基化的人CAMP启动子活性显著高于甲基化的启动子活性。这些结果提示，人CAMP/LL-37基因可能在口腔鳞癌中起抑癌作用，DNA甲基化可能通过直接下调人CAMP启动子活性而在口腔鳞癌发生中发挥作用。
LL-37, the active product of human cathelicidin antimicrobial peptide (CAMP) has a broad spectrum of antibacterial activity. LL-37 also has important physiological functions in immune regulation, angiogenesis and in modulating apoptosis. The roles of LL-37 in oral squamous cell carcinoma (OSCC) are still not clear. The correlation between DNA methylation and human CAMP expression is also unknown. Here human CAMP/LL-37 expression was assessed by immunohistochemistry in normal and OSCC tissues. The results indicated that low expression of CAMP/LL-37 correlated with histological differentiation and lymph node metastasis and also promoted tumor progression. A cell-specific methylation pattern in the promoter region of human CAMP was detected. Treatment with 5-aza-2′-deoxycytidine, a DNA demethylation reagent can increase human CAMP expression in epithelial cancer cells. The reporter assay showed that unmethylated human CAMP promoter activity was significantly higher than methylated promoter activity. Taken together, these results suggested that human CAMP/LL-37 might act as a tumor-suppressor in OSCC and DNA methylation might play roles during carcinogenesis via directly downregulating human CAMP promoter activity.