Inactivation Of CYB5R2 By Promoter Hypermethylation In Nasopharyneal Carcinoma

The etiology of nasopharyngeal carcinoma (NPC) is multi-factorial,including latent infection of Epstein-Barr Virus (EBV), environmental factors, dietary habits, familial heredity etc. It has been shown that inactivation of tumor suppressor genes (TSG) plays an important role in NPC. Aberrant DNA methylation of CpG islands is an important mechanism for epigenetic inactivation of TSGs.To identify novel candidate tumor suppressor genes silenced by DNA hypermethylation in NPC, in our previous study, we analyzed the global expression restoration in the NPC cell lines-CNE2 and HONE1, after the treatment with 5-aza-dC and TSA by performing a genome-wide screening. CYB5R2 (cytochrome b5 reductase b5R.2) was up-regulated 24 and 19 folds respectively after the treatment. In this study, we confirm our resluts by RT-PCR, methylation specific PCR. Our data showed that CYB5R2 expression was down-regulated in NPC cell lines and primary tumors compared with normal nasopharyngeal epithelia. Promoter methylation of CYB5R2 could be observed in 100% (6/6) of the NPC cell lines and 84% (42/50) of primary tumors, but not in any of the normal epithelia. We further confirmed that 5-aza-dC can restore the transpription of CYB5R2 in 4 NPC cell lines. Thus, out data demonstrated that CYB5R2 is frequently inactivated by promoter methylation in NPC.