title: EZH2 promotes invasion and metastasis of laryngeal squamous cells carcinoma via epithelial-mesenchymal transition through H3K27me3.
abstract: Enhancer of Zeste Homolog 2(EZH2), which can change chromatin structure by tri-methylation of the 27th lysine of H3 in nucleosome histone (H3K27me3), is involved in different types of cancers. However, the role and mechanism underlying aberrant EZH2 expression in laryngeal squamous cells carcinoma (LSCC) remain unclear. In the present study, we found that down-regulation of EZH2 and H3K27me3 in LSCC cells (Hep-2 and SCC10A) resulted in an mesenchymal-epithelial transition(MET) like cell morphology and lower invasion in vitro, weakened tumor growth, intrahepatic and pulmonary metastasis in vivo. Furthermore, EZH2 promoted the epithelial-mesenchymal transition(EMT) process through down-regulation of Ca2+dependent cell adhesion molecule E (E-cadherin) and up-regulation of H3K27me3 in vitro and in vivo. Moreover, E-cadherin was transcriptionally induced upon stable knockdown of EZH2, and quantitative chromatin immunoprecipitation(qChIP) analysis confirmed the depletion of H3K27me3 enrichment on E-cadherin promoter upon EZH2 knockdown in Hep-2 and SCC10A cells. In addition, the expression of EZH2 was positively correlated with that of H3K27me3 and both of them were inversely correlated with E-cadherin expression in human LSCC tissues. In summary, this study indicated that EZH2 promoted invasion and metastasis of LSCC via EMT through H3K27me3.
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi Wu Road #157, Xi'an 710004, Shan'xi Province, China.
authors.forename: HuaNan
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Xi'an Xd Group Hospital, Feng Deng Road #97, Xi'an 710077, Shan'xi Province, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi Wu Road #157, Xi'an 710004, Shan'xi Province, China.
authors.forename: SiJing
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Xi'an Children's Hospital, West of the Hospital Lane #69, Xi'an 710003, Shan'xi Province, China.
authors.forename: HuanHuan
authors.initials: H
authors.lastname: Chang
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Xi'an Center Hospital, Xi Wu Road #161, Xi'an 710004, Shan'xi Province, China.
authors.forename: ChunXi
authors.initials: C
authors.lastname: Yi
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, The First Affiliated Hospital of Xi'an Medical University, Feng Gao Road #69, Xi'an 710077, Shan'xi Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi Wu Road #157, Xi'an 710004, Shan'xi Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi Wu Road #157, Xi'an 710004, Shan'xi Province, China.
authors.forename: HaiLi
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi Wu Road #157, Xi'an 710004, Shan'xi Province, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi Wu Road #157, Xi'an 710004, Shan'xi Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi Wu Road #157, Xi'an 710004, Shan'xi Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi Wu Road #157, Xi'an 710004, Shan'xi Province, China. Electronic address: renxiaoyong@vip.126.com.
authors.forename: XiaoYong
authors.initials: X
authors.lastname: Ren
mesh_terms: D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000378:metabolism*; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D006657:Histones; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D002118:Calcium
keywords: EZH2; Epithelial-mesenchymal transition; H3K27me3; Laryngeal squamous cells carcinoma; Metastasis