title: The polycomb group protein EZH2 is a novel therapeutic target in tongue cancer.
abstract: EZH2, a core member of the Polycomb Repressor Complex 2 (PRC2), mediates transcriptional silencing by catalyzing the trimethylation of histone 3 lysine 27 (H3K27), which plays key roles in cancer initiation and progression. Here, we investigated the expression pattern and biological roles of EZH2 in tongue tumorigenesis by loss-of-function assays using small interference RNA and EZH2 inhibitor DZNep. Also we determined the therapeutic efficiency of DZNep against tongue cancer in vivo. We found that aberrantly overexpressed EZH2 was associated with pathological grade, cervical nodes metastasis and Ki-67 expression in tongue cancers. Elevated EZH2 correlated with shorter overall survival and showed significant and independent prognostic importance in patients with tongue cancer. Both genetic and pharmacological depletion of EZH2 inhibited cell proliferation, migration, invasion and colony formation and decreased CD44+ subpopulation probably in part through modulating p16, p21 and E-caherin. Moreover, DZNep enhanced the anticancer effects of 5-Fluorouracil. Furthermore, intratumoral EZH2 inhibition induced by DZNep intraperitoneal administration significantly attenuated tumor growth in a tongue cancer xenograft model. Taken together, our results indicate that EZH2 serves as a key driver with multiple oncogenic functions during tongue tumorigenesis and a new biomarker for tongue cancer diagnosis and prognostic prediction. These findings open up possibilities for therapeutic intervention against EZH2 in tongue cancer.
authors.affiliation: Head Neck Cancer Center, Institute of Stomatology, Affiliated Stomatological Hospital, Nanjing Medical University, Jiangsu, China PRC.
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Li
authors.forename: Yanling
authors.initials: Y
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Qiu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Chunping
authors.initials: C
authors.lastname: Yuan
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Dongmiao
authors.initials: D
authors.lastname: Wang
authors.forename: Jinhai
authors.initials: J
authors.lastname: Ye
authors.forename: Hongbin
authors.initials: H
authors.lastname: Jiang
authors.forename: Jianrong
authors.initials: J
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D063151:Polycomb Repressive Complex 2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011897:Random Allocation; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D034741:RNA, Small Interfering; C048460:3-deazaneplanocin; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D000241:Adenosine