title: Upregulation of Ying Yang 1 (YY1) suppresses esophageal squamous cell carcinoma development through heme oxygenase-1.
abstract: Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies worldwide. Ying Yang 1 (YY1), a ubiquitously expressed GLI-Krüppel zinc finger transcription factor, plays a regulatory role in a variety of fundamental biological processes, such as embryonic development, growth, apoptosis, differentiation and oncogenic transformation. The purpose of this study was to investigate the expression of YY1 in normal and cancerous esophageal tissues and its function in ESCC development. We found that the expression of YY1 mRNA was significantly increased in the tumor tissues, compared with the para-tissues or normal esophageal tissues. The increased expression of YY1 in tumor samples was further confirmed by immunohistochemistry. Furthermore, the overexpression of YY1 conferred radioresistance to the ESCC TE-1 cells and resulted in markedly reduced cell proliferation. Accordingly, the small interfering RNA-mediated silencing of YY1 expression in TE-1 cells resulted in increased proliferation by enhancing the binding of P21 to Cyclin D1 and CDK4, a protein complex known to mediate cell cycle progression. Moreover, besides P21, heme oxygenase-1 (HO-1) was identified as a YY1 downstream effector, as YY1 stimulated HO-1 expression in esophageal cancer cells. YY1 mediated biological function through transcription of HO-1. Forced expression of HO-1 could moderately suppress proliferation of TE-1 cells. The expression of YY1 significantly correlated with that of HO-1 in ESCC tissues. Taken together, we demonstrated overexpression of YY1 in esophageal carcinoma and identified HO-1 as its target.
authors.affiliation: Department of Radiotherapy, Changzhou Tumor Hospital, Soochow University, Changzhou, China; Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China.
authors.forename: Judong
authors.initials: J
authors.lastname: Luo
authors.forename: Xifa
authors.initials: X
authors.lastname: Zhou
authors.forename: Xin
authors.initials: X
authors.lastname: Ge
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
authors.forename: Jianping
authors.initials: J
authors.lastname: Cao
authors.forename: Xujing
authors.initials: X
authors.lastname: Lu
authors.forename: Yang
authors.initials: Y
authors.lastname: Ling
authors.forename: Shuyu
authors.initials: S
authors.lastname: Zhang
mesh_terms: D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000528:radiation effects; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011836:Radiation Tolerance; D015854:Up-Regulation; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
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