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DNA methylation directly downregulates human cathelicidin antimicrobial peptide gene (CAMP) promoter activity

2017; Impact Journals LLC; Volume: 8; Issue: 17 Linguagem: Inglês

10.18632/oncotarget.15847

1949-2553

Xi Chen, Guangying Qi, Mingqun Qin, Zou Yantao, Kanghua Zhong, Ying Tang, Yong Guo, Xin-Xiang Jiang, Lihua Liang, Xianqiong Zou,

Pediatric health and respiratory diseases

// Xi Chen 1, * , Guangying Qi 2, 4, * , Mingqun Qin 3, * , Yantao Zou 1 , Kanghua Zhong 1 , Ying Tang 1 , Yong Guo 1 , Xinxiang Jiang 3 , Lihua Liang 3 , Xianqiong Zou 1 1 College of Biotechnology, Guilin Medical University, Guilin 541100, Guangxi, P. R. China 2 Department of Pathology and Physiopathology, Guilin Medical University, Guilin 541004, Guangxi, P. R. China 3 Department of Stomatology, Affiliated Hospital of Guilin Medical University, Guilin 541004, Guangxi, P. R. China 4 Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin 541004, Guangxi, P. R. China * These authors contributed equally to this work Correspondence to: Xianqiong Zou, email: xianqiongzou2009@yahoo.com Keywords: CAMP, LL-37, OSCC, DNA methylation, promoter Received: September 01, 2016 Accepted: February 20, 2017 Published: March 02, 2017 ABSTRACT 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.