PMID- 27450916 OWN - NLM STAT- MEDLINE DCOM- 20170206 LR - 20170206 IS - 1879-0038 (Electronic) IS - 0378-1119 (Linking) VI - 593 IP - 2 DP - 2016 Nov 30 TI - Promoter hypermethylation of miR-34a contributes to the risk, progression, metastasis and poor survival of laryngeal squamous cell carcinoma. PG - 272-6 LID - S0378-1119(16)30573-X [pii] LID - 10.1016/j.gene.2016.07.047 [doi] AB - 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. CI - Copyright (c) 2016 Elsevier B.V. All rights reserved. FAU - Shen, Zhisen AU - Shen Z AD - Lihuili Hospital of Ningbo University, Ningbo 315040, China. Electronic address: szs7216@163.com. FAU - Zhou, Chongchang AU - Zhou C AD - Lihuili Hospital of Ningbo University, Ningbo 315040, China; The Medical School of Ningbo University, Ningbo 315211, China. FAU - Li, Jinyun AU - Li J AD - The Medical School of Ningbo University, Ningbo 315211, China. FAU - Ye, Dong AU - Ye D AD - Lihuili Hospital of Ningbo University, Ningbo 315040, China. FAU - Li, Qun AU - Li Q AD - Lihuili Hospital of Ningbo University, Ningbo 315040, China. FAU - Wang, Jian AU - Wang J AD - Lihuili Hospital of Ningbo University, Ningbo 315040, China; The Medical School of Ningbo University, Ningbo 315211, China. FAU - Cui, Xiang AU - Cui X AD - Lihuili Hospital of Ningbo University, Ningbo 315040, China; The Medical School of Ningbo University, Ningbo 315211, China. FAU - Chen, Xiaoying AU - Chen X AD - The Medical School of Ningbo University, Ningbo 315211, China. FAU - Bao, Tianlian AU - Bao T AD - The Medical School of Ningbo University, Ningbo 315211, China. FAU - Duan, Shiwei AU - Duan S AD - The Medical School of Ningbo University, Ningbo 315211, China. Electronic address: duanshiwei@nbu.edu.cn. LA - eng PT - Journal Article DEP - 20160720 PL - Netherlands TA - Gene JT - Gene JID - 7706761 RN - 0 (Biomarkers, Tumor) RN - 0 (MIRN34 microRNA, human) RN - 0 (MicroRNAs) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/*genetics MH - Carcinoma, Squamous Cell/*genetics/pathology MH - *DNA Methylation MH - Female MH - Genetic Predisposition to Disease MH - Humans MH - Laryngeal Neoplasms/*genetics/pathology MH - Lymphatic Metastasis MH - Male MH - MicroRNAs/*genetics MH - Middle Aged MH - Promoter Regions, Genetic OTO - NOTNLM OT - DNA methylation OT - LSCC OT - Prognosis OT - Promoter OT - miR-34a EDAT- 2016/07/28 06:00 MHDA- 2017/02/07 06:00 CRDT- 2016/07/25 06:00 PHST- 2016/01/19 00:00 [received] PHST- 2016/07/15 00:00 [revised] PHST- 2016/07/19 00:00 [accepted] PHST- 2016/07/25 06:00 [entrez] PHST- 2016/07/28 06:00 [pubmed] PHST- 2017/02/07 06:00 [medline] AID - S0378-1119(16)30573-X [pii] AID - 10.1016/j.gene.2016.07.047 [doi] PST - ppublish SO - Gene. 2016 Nov 30;593(2):272-6. doi: 10.1016/j.gene.2016.07.047. Epub 2016 Jul 20.