Frequent epigenetic inactivation of Myocardin in human nasopharyngeal carcinoma.
BACKGROUND
Epigenetic silencing of tumor suppressor genes plays an important role in nasopharyngeal carcinoma (NPC) tumorigenesis. In the present study, we explore a novel target gene of epigenetic silencing in NPC, Myocardin, which is inactivated by promoter hypermethylation.


METHODS
Transcriptional expression levels of Myocardin were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Methylation status was addressed by methylation-specific PCR and bisulfite genomic sequencing.


RESULTS
Myocardin mRNA expression was inactivated in 4 of 5 NPC cell lines. Myocardin was aberrantly methylated in 4 of 5 NPC cell lines (80%) and in 48 of 65 NPC primary tumors (73.8%, but not in any of the 12 normal nasopharyngeal tissues tested. Myocardin expression could be reactivated in NPC cells after treatment with the demethylating agent 5-aza-2'-deoxycytidine (5-aza-dC).


CONCLUSIONS
Epigenetic inactivation of Myocardin is a frequent and tumor-specific event in NPC. Our findings suggest that Myocardin is a candidate tumor suppressor gene in NPC.
Chen
Fu
F
Department of Radiation Oncology, Eye Ear Nose and Throat Hospital of Fudan University, Shanghai, China.
Mo
Yingxi
Y
Ding
Hao
H
Xiao
Xue
X
Wang
Shu Yi
SY
Huang
Guangwu
G
Zhang
Zhe
Z
Wang
Sheng Zi
SZ
D000368:Aged; D002277:Carcinoma; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D019175:DNA Methylation / Q000235:genetics*; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D000099251:Myocardin
D009687:Nuclear Proteins; D015534:Trans-Activators; D000099251:Myocardin