Study On Methylation Of PCDH8Gene In Nasopharyngeal Carcinoma

Background: Protocadherin8(PCDH8), was reported to be a tumorsuppressor involved in tumorigenesis in cancers. We aimed to investigate theepigenetic inactivation of PCDH8and its tumor suppressor effect innasopharyngeal carcinoma (NPC).Methods: The expression level of PCDH8mRNA was detected in NPCcell lines C666-1, CNE1, HK1, HNE1, HONE1, One immortalized butnontransformed nasopharyngeal epithelial Cell line (NP69) and onehypopharyngeal carcinoma cell line (Fadu) by reversetranscription-polymerase chain reaction (RT-PCR). MSP (methyaltioinspecific PCR) was used to measure the promoter methylation status of celllines,41cases of nasopharyngeal carcinoma tissues and16cases of chronicnasopharyngitis tissues. The tumor-suppressive role of PCDH8in NPC wasstudied by re-introducing PCDH8expression in NPC cell line CNE1.Results: NP69and Fadu cells showed stable PCDH8expression, whilethere was weak expression in HK1, HNE1cells and absent expression inremaining detected NPC cell lines. Promoter methylation of PCDH8genewas detected in all NPC cell lines, Fadu cells and NPC tissues in which the frequency of promoter methylation was85.3%(35/41). However,methylation of PCDH8promoter was not found in NP69cells and chronicnasopharyngitis tissues. The methylation of PCDH8promoter innasopharyngeal carcinoma was not correlated with all the clinicalpathological characters. Treatment of NPC cell lines with5-aza-2’-deoxycytidine (Aza) and trichostatin A (TSA) could restore PCDH8expression. Ectopic expression of PCDH8in NPC cell line CNE1significantly inhibited cell colony formation and cell migration.Conclusions: For the first time, our study demonstrates the epigeneticinactivation of PCDH8by promoter methylation and its tumor-suppresivefunction in NPC. Thus, PCDH8could be identified as a tumor suppressor inNPC.