title: YY1 is a novel potential therapeutic target for the treatment of HPV infection-induced cervical cancer by arsenic trioxide.
abstract: OBJECTIVE
  YY1 is a zinc finger transcription factor involved in the regulation of cell growth, development, and differentiation. Although YY1 can regulate human papillomavirus-type (HPV) viral oncogenes E6 and E7, it remains unknown if YY1 plays a key role in carcinoma progression of HPV-infected cells. Here we sought to determine whether YY1 is upregulated in the cervical cancer tissues and YY1 inhibition contributes to apoptosis of cervical cancer cells, which is at least partly p53 dependent. Therefore, YY1 can be a potential therapeutic target for cervical cancer treatment by arsenic trioxide (As2O3).
  
  
  METHODS
  The expression level of YY1 was examined and analyzed by Western blot in pathologically confirmed primary cervical cancer samples, in the adjacent normal samples, as well as in normal cervix samples. The effects of YY1 inhibition by specific small interfering RNA in HeLa cells were determined by Western blot analysis of p53 level, cell growth curve, colony formation assay, and apoptosis. The contribution of YY1 to As2O3-induced p53 activation and apoptosis was also examined by Western blot and cell cycle analysis.
  
  
  RESULTS
  Here we report that the expression level of YY1 is significantly elevated in the primary cancer tissues. In HPV-positive HeLa cells, small interfering RNA-mediated YY1 inhibition induced apoptosis and increased the expression of p53. Treatment of HeLa cells with As2O3, a known anti-cervical cancer agent, reduced both protein and mRNA levels of YY1 in HeLa cells. YY1 knockdown significantly further enhanced As2O3-induced apoptosis.
  
  
  CONCLUSIONS
  These results demonstrated that the expression of YY1 is upregulated in cervical carcinomas and that YY1 plays a critical role in the progression of HPV-positive cervical cancer. In addition, YY1 inhibition induces p53 activation and apoptosis in HPV-infected HeLa cells. Thus, YY1 is an As2O3 target and could serve as a potential drug sensitizer for anti-cervical cancer therapy.
authors.affiliation: Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Guifen
authors.initials: G
authors.lastname: He
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wu
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.forename: Nadire
authors.initials: N
authors.lastname: Duru
authors.forename: Xiangtao
authors.initials: X
authors.lastname: Kong
authors.forename: Pingzhao
authors.initials: P
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Wan
authors.forename: Long
authors.initials: L
authors.lastname: Sui
authors.forename: Qisang
authors.initials: Q
authors.lastname: Guo
authors.forename: Jian-Jian
authors.initials: JJ
authors.lastname: Li
authors.forename: Long
authors.initials: L
authors.lastname: Yu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D017931:DNA Primers; D005260:Female; D006367:HeLa Cells; D052162:Human papillomavirus 16; D006801:Humans; D010087:Oxides / Q000008:administration & dosage; D030361:Papillomavirus Infections / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D050986:YY1 Transcription Factor / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D017931:DNA Primers; D010087:Oxides; D012333:RNA, Messenger; D050986:YY1 Transcription Factor; D000077237:Arsenic Trioxide