Frequent epigenetic inactivation of Myocardin in human nasopharyngeal carcinoma.

Abstract

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. 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. 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). 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.