3-Deazaneplanocin A suppresses aggressive phenotype-related gene expression in an oral squamous cell carcinoma cell line.
In tumor tissues, alterations of gene expression caused by aberrant epigenetic modifications confer phenotypic diversity on malignant cells. Although 3-deazaneplanocin A (DZNep) has been shown to reactivate tumor suppressor genes in several cancer cells, it remains unclear whether DZNep attenuates the malignant phenotypes of oral squamous cell carcinoma (OSCC) cells. In this study, we investigated the effect of DZNep on the expression of genes related to aggressive phenotypes, such as epithelial-mesenchymal transition, in OSCC cells. We found that DZNep reduced the cellular levels of polycomb group proteins (EZH2, SUZ12, BMI1, and RING1A) and the associated trimethylation of Lys27 on histone H3 and monoubiquitination of Lys119 on histone H2A in the poorly differentiated OSCC cell line SAS. Immunocytochemical staining demonstrated that DZNep induced the reorganization of filamentous actin and the membrane localization of E-cadherin associated with cell-cell adhesions. We also found an inhibitory effect of DZNep on cell proliferation using a WST assay. Finally, quantitative RT-PCR analysis demonstrated that genes involved in the aggressive phenotypes (TWIST2, EGFR, ACTA2, TGFB1, WNT5B, and APLIN) were down-regulated, whereas epithelial phenotype genes (CDH1, CLDN4, IVL, and TGM1) were up-regulated in SAS cells treated with DZNep. Collectively, our findings suggest that DZNep reverses the aggressive characteristics of OSCC cells through the dynamic regulation of epithelial plasticity via the reprogramming of gene expression patterns.
Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, Japan. Electronic address: hatta@college.fdcnet.ac.jp.
Mitsutoki
M
Hatta
Department of Oral and Maxillofacial Surgery, Fukuoka Dental College, Fukuoka, Japan.
Kaori
K
Naganuma
Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, Japan.
Kenichi
K
Kato
Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, Japan.
Jun
J
Yamazaki
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006657:Histones / Q000032:analysis; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D063146:Polycomb-Group Proteins / Q000032:analysis
D000970:Antineoplastic Agents; D006657:Histones; D063146:Polycomb-Group Proteins; C048460:3-deazaneplanocin; D000241:Adenosine
3-Deazaneplanocin A; Epithelial–mesenchymal transition; Histone modifications; Oral squamous cell carcinoma; Polycomb group protein