title: EZH2 elevates the proliferation of human cholangiocarcinoma cells through the downregulation of RUNX3.
abstract: To investigate the impact of histone methyltransferase enhancer of zeste homolog 2 (EZH2) on the proliferation and apoptosis of human cholangiocarcinoma cells as well as its related mechanisms. Immunohistochemistry and Western blot analyses were used to examine the expression of EZH2 in 40 cases of human cholangiocarcinoma tissues and four strains of human cholangiocarcinoma cells. The influence of EZH2 on cell growth and apoptosis were assessed by knockdown experiments, and a xenograft experiment in nude mice was performed to evaluate the impact of siEZH2 on the tumorigenicity of tumor cells. The correlation of EZH2, clinic pathological features and overall survival rates was also analyzed. EZH2 was highly expressed in human cholangiocarcinoma tissues and cells. Silencing of EZH2 could significantly reduce the methylation level of RUNX3 DNA in human cholangiocarcinoma cells and improve its protein expression as well as inhibit cell proliferation, induce apoptosis and slow down the growth of tumor in nude mice. In addition, the expression of EZH2 was associated with the tumor stage, lymph node positivity and poor prognoses. Overexpression of EZH2 can promote the proliferation of cholangiocarcinoma cells and inhibit their apoptosis. It is associated with poor prognoses in patients with cholangiocarcinoma. Therefore, EZH2 could be a potential clinical therapeutic target for the treatment of cholangiocarcinoma.
authors.affiliation: Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, 541001, Guangxi, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.forename: Jian
authors.initials: J
authors.lastname: Du
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Tang
authors.forename: Zhenran
authors.initials: Z
authors.lastname: Wang
authors.forename: Songqing
authors.initials: S
authors.lastname: He
mesh_terms: D000368:Aged; D000818:Animals; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D049109:Cell Proliferation / Q000502:physiology; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000378:metabolism*; D050677:Core Binding Factor Alpha 3 Subunit / Q000096:biosynthesis*; D015536:Down-Regulation / Q000502:physiology*; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D063151:Polycomb Repressive Complex 2 / Q000096:biosynthesis*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D050677:Core Binding Factor Alpha 3 Subunit; C493729:Runx3 protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2