Promoter hypermethylation of miR-34a contributes to the risk, progression, metastasis and poor survival of laryngeal squamous cell carcinoma

作者：Shen, Zhisen^*; Zhou, Chongchang; Li, Jinyun; Ye, Dong; Li, Qun; Wang, Jian; Cui, Xiang; Chen, Xiaoying; Bao, Tianlian; Duan, Shiwei^*

来源：Gene, 2016, 593(2): 272-276.

DOI：10.1016/j.gene.2016.07.047

• LSCC
• miR-34a
• DNA methylation
• Promoter
• Prognosis

MiR-34a is a direct transcriptional target of p53, which induces cell cycle arrest, senescence, and apoptosis. Recently, we and others identified abnormal expression of miR-34a in laryngeal squamous cell carcinoma (LSCC). The aim of our present study was to investigate the contribution of miR-34a promoter methylation to LSCC. Bisulfite pyrosequencing technology was applied to measure DNA methylation levels of six CpG sites in the miR-34a promoter from 104 LSCC tumor tissues and their corresponding adjacent tissues. Our results showed that the methylation levels of the miR-34a promoter were significantly higher in cancer tissues compared with the adjacent tissues (adjusted P = 5.05E-10). A breakdown analysis for cigarette smoking behavior indicated a significantly elevated tendency of miR-34a methylation level in LSCC patients with smoking behavior but not in LSCC patients without smoking behavior (Smoking: Tumor vs Normal, adjusted P = 3.12E-9; Non-smoking: Tumor vs Normal, adjusted P = 0.073). In addition, miR-34a promoter methylation frequency remarkably increased in the advanced stage patients (adjusted P = 0.003) and advanced T classified tumors (adjusted P = 0.015). Moreover, significant association of miR-34a promoter hypermethylation with LSCC lymph metastasis was observed (adjusted P = 0.002). Meanwhile, Kaplan-Meier survival curves results showed that high methylation of miR-34a promoter were associated with poor overall survival (log-rank test, P = 0.023). Our study revealed that miR-34a promoter hypermethylation was a risk factor for LSCC, played a critical role in the disease progression and metastasis, and could serve as a poor prognostic factor for LSCC.

• 出版日期2016-11-30
• 单位宁波市医疗中心李惠利医院; 宁波大学