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

• Published in: Gene 2016-11, Vol.593 (2), p.272-276
• Main Authors: Shen, Zhisen, Zhou, Chongchang, Li, Jinyun, Ye, Dong, Li, Qun, Wang, Jian, Cui, Xiang, Chen, Xiaoying, Bao, Tianlian, Duan, Shiwei
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; DNA Methylation; Female; Genetic Predisposition to Disease; Humans; Laryngeal Neoplasms - genetics; Laryngeal Neoplasms - pathology; LSCC; Lymphatic Metastasis; Male; MicroRNAs - genetics; Middle Aged; miR-34a; Prognosis; Promoter; Promoter Regions, Genetic
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2016.07.047

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. •The hypermethylation of miR-34a promoter is a common event in laryngeal squamous cell carcinoma.•The methylation of miR-34a is involved in the progression and lymph metastasis of laryngeal squamous cell carcinoma.•The methylated miR-34a promoter is a prognostic factor for laryngeal squamous cell carcinoma.