title: Human papillomavirus promotes esophageal squamous cell carcinoma by regulating DNA methylation and expression of HLA-DQB1.
abstract: OBJECTIVE
  Esophageal cancer (EC) is one of the most prevalent and deadly cancers worldwide. Along with nutrition, smoking and alcohol consumption, human papillomavirus (HPV) infection is one of the major risk factors, which is modulated by host immune response. This study is aimed at elucidating how HPV modifies host immune system in the EC pathogenesis.
  
  
  METHODS
  The HPV and HLA-DQB1 levels in primary esophageal squamous cell (ESC) cancer cells from Han, Khazak and Uygur patients were analyzed by quantitative real-time PCR and immunoblotting. The ability of HPV16 E6/E7 to transform normal primary ESCs was investigated by infecting ESC with pMSCVpuro-carried E6 or E7. The shRNA against HPV16 E6 or E7 was delivered by adenovirus into esophageal squamous cell carcinoma (ESCC) cells with high HPV content. The DNA methylation level of HLA-DQB1 was measured by methylation-specific PCR.
  
  
  RESULTS
  The HLA-DQB1 expression level was correlated with the levels of HPV and inversely related to DNA methylation level of HLA-DQB1. Overexpressing HPV16 E6 or E7 alone was enough to transform normal primary ESCs. However, single knockdown of either E6 or E7 in ESC cancer cells did not reduce HLA-DQB1 expression.
  
  
  CONCLUSIONS
  Oncogenic HPV E6 and E7 genes promoted ESCC pathogenesis by upregulating susceptible HLA-DQB1 via DNA demethylation.
authors.affiliation: Department of Thoracic Surgery, Xinjiang Medical University, First Affiliated Hospital, Urumqi, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Feng
authors.forename: Idiris
authors.initials: I
authors.lastname: Awuti
authors.forename: Yanchao
authors.initials: Y
authors.lastname: Deng
authors.forename: Desheng
authors.initials: D
authors.lastname: Li
authors.forename: Maidiniyeti
authors.initials: M
authors.lastname: Niyazi
authors.forename: Julaiti
authors.initials: J
authors.lastname: Aniwar
authors.forename: Ilyar
authors.initials: I
authors.lastname: Sheyhidin
authors.forename: Guoqing
authors.initials: G
authors.lastname: Lu
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Liwei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology* / Q000821:virology*; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000821:virology*; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000096:biosynthesis*; D006801:Humans; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: DNA methylation; HLA-DQB1; HPV; esophageal squamous cell cancer