EZH2 promotes invasion and metastasis of laryngeal squamous cells carcinoma via epithelial-mesenchymal transition through H3K27me3

Autor: Hua-Nan Luo, SiJing Ma, Hai-Li Guo, Ying Gao, Hui Cao, Ying Sheng, Jin Hou, Yuan Jiang, Chunxi Yi, Xiaoyong Ren, HuanHuan Chang, Jing Yan
Rok vydání: 2016
Předmět:
0301 basic medicine
Epithelial-Mesenchymal Transition
Biophysics
Mice
Nude
macromolecular substances
Real-Time Polymerase Chain Reaction
Cell morphology
Biochemistry
Histones
Mice
03 medical and health sciences
0302 clinical medicine
Antigens
CD
Cell Line
Tumor
Animals
Humans
Enhancer of Zeste Homolog 2 Protein
Neoplasm Invasiveness
Epithelial–mesenchymal transition
Neoplasm Metastasis
Promoter Regions
Genetic
Laryngeal Neoplasms
Molecular Biology
Gene knockdown
biology
Cell adhesion molecule
EZH2
Cell Biology
Cadherins
Immunohistochemistry
Chromatin
Gene Expression Regulation
Neoplastic
030104 developmental biology
Histone
Gene Knockdown Techniques
Lymphatic Metastasis
030220 oncology & carcinogenesis
Carcinoma
Squamous Cell
biology.protein
Cancer research
Calcium
Chromatin immunoprecipitation
Zdroj: Biochemical and Biophysical Research Communications. 479:253-259
ISSN: 0006-291X
DOI: 10.1016/j.bbrc.2016.09.055
Popis: 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.
Databáze: OpenAIRE
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