PMID- 25452816
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 9
IP  - 1
DP  - 2015 Jan
TI  - Clinical significance of epigenetic silencing and re-expression of 
      O6-methylguanine-DNA methyltransferase using epigenetic agents in laryngeal 
      carcinoma.
PG  - 35-42
AB  - The aim of the present study was to investigate the association between 
      O6-methylguanine-DNA methyltransferase (MGMT) gene expression levels, and DNA 
      methylation status and histone modifications in laryngeal squamous cell carcinoma 
      (LSCC). Chromatin immunoprecipitation, methylation-specific polymerase chain 
      reaction (PCR), and reverse transcription-quantitative PCR were performed to 
      analyze histone modifications, DNA methylation status and mRNA expression levels 
      in the promoter region of the MGMT gene in laryngeal carcinoma HEp-2 cells, as 
      well as in 50 paired healthy and LSCC tissue samples. The present study 
      demonstrated that treatment of HEp-2 cells with 5-aza-2'-deoxycytidine (Aza), a 
      DNA methyltransferase inhibitor, significantly upregulated MGMT mRNA expression 
      levels, reduced MGMT DNA methylation, reduced MGMT histone H3 lysine 9 (H3K9) 
      di-methylation, and increased MGMT histone H3 lysine 4 di-methylation without a 
      significant change in H3K9 acetylation. Trichostatin A (TSA), a histone 
      deacetylase inhibitor, marginally upregulated MGMT mRNA expression levels without 
      affecting the DNA methylation status, or H3K9 or H3K4 di-methylation, however, 
      TSA treatment caused a significant increase in H3K9 acetylation. Furthermore, Aza 
      and TSA combination treatment produced a synergistic effect. In the LSCC samples, 
      the rate of DNA methylation in the MGMT gene was 54%, compared with 24% in the 
      healthy control group (P<0.05). Therefore, data from the present study indicates 
      that MGMT may serve as a novel therapeutic target in the treatment of LSCC.
FAU - Yang, Jing
AU  - Yang J
AD  - Department of Otorhinolaryngology, Shengjing Hospital of China Medical 
      University, Shenyang, Liaoning 110004, P.R. China.
FAU - Zhu, Xin-Bing
AU  - Zhu XB
AD  - Department of General Sugery, General Hospital of Liaohe Oil Field, Panjin, 
      Liaoning 124010, P.R. China.
FAU - He, Li-Xia
AU  - He LX
AD  - Department of Otorhinolaryngology, Fushun Second Hospital, Fushun, Liaoning 
      113001, P.R. China.
FAU - Gu, Zhao-Wei
AU  - Gu ZW
AD  - Department of Otorhinolaryngology, Shengjing Hospital of China Medical 
      University, Shenyang, Liaoning 110004, P.R. China.
FAU - Jin, Ming-Zhu
AU  - Jin MZ
AD  - Department of Otorhinolaryngology, Shengjing Hospital of China Medical 
      University, Shenyang, Liaoning 110004, P.R. China.
FAU - Ji, Wen-Yue
AU  - Ji WY
AD  - Department of Otorhinolaryngology, Shengjing Hospital of China Medical 
      University, Shenyang, Liaoning 110004, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20141103
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC4247240
OTO - NOTNLM
OT  - 5-aza-2'-deoxycytidine
OT  - DNA methylation
OT  - O6-methylguanine-DNA methyltransferase gene
OT  - histone modification
OT  - laryngeal carcinoma
OT  - trichostatin A
EDAT- 2014/12/03 06:00
MHDA- 2014/12/03 06:01
PMCR- 2014/11/03
CRDT- 2014/12/03 06:00
PHST- 2014/04/09 00:00 [received]
PHST- 2014/09/16 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2014/12/03 06:01 [medline]
PHST- 2014/11/03 00:00 [pmc-release]
AID - ol-09-01-0035 [pii]
AID - 10.3892/ol.2014.2662 [doi]
PST - ppublish
SO  - Oncol Lett. 2015 Jan;9(1):35-42. doi: 10.3892/ol.2014.2662. Epub 2014 Nov 3.