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Journal of cellular physiology v.233 no.10, 2018년, pp.6565 - 6577  

Tumor‐suppressive roles of ΔNp63β‐miR‐205 axis in epithelial–mesenchymal transition of oral squamous cell carcinoma via targeting ZEB1 and ZEB2

Hashiguchi, Yuma (Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan ) ; Kawano, Shintaro (Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan ) ; Goto, Yuichi (Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Rehabilitation, Course for Developmental Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan ) ; Yasuda, Kaori (Cell Innovator, Inc., Venture Business Laboratory of Kyushu University, Fukuoka, Japan ) ; Kaneko, Naoki (Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan ) ; Sakamoto, Taiki ; Matsubara, Ryota ; Jinno, Teppei ; Maruse, Yasuyuki ; Tanaka, Hideaki ; Morioka, Masahiko ; Hattori, Taichi ; Tanaka, Shoichi ; Kiyoshima, Tamotsu ; Nakamura, Seiji ;
  • 초록  

    We previously revealed that epithelial‐to‐mesenchymal transition (EMT) was mediated by ΔNp63β, a splicing variant of ΔNp63, in oral squamous cell carcinoma (OSCC). Recent studies have highlighted the involvement of microRNA (miRNA) in EMT of cancer cells, though the mechanism remains unclear. To identify miRNAs responsible for ΔNp63β‐mediated EMT, miRNA microarray analyses were performed by ΔNp63β‐overexpression in OSCC cells; SQUU‐B, which lacks ΔNp63 expression and displays EMT phenotypes. miRNAs microarray analyses revealed miR‐205 was the most up‐regulated following ΔNp63β‐overexpression. In OSCC cells, miR‐205 expression was positively associated with ΔNp63 and negatively with zinc‐finger E‐box binding homeobox (ZEB) 1 and ZEB2, potential targets of miR‐205. miR‐205 overexpression by miR‐205 mimic transfection into SQUU‐B cells led to decreasing ZEB1, ZEB2, and mesenchymal markers, increasing epithelial markers, and reducing cell motilities, suggesting inhibition of EMT phenotype. Interestingly, the results opposite to this phenomenon were obtained by transfection of miR‐205 inhibitor into OSCC cells, which express ΔNp63 and miR‐205. Furthermore, target protector analyses revealed direct regulation by miR‐205 of ZEB1 and ZEB2 expression. These results showed tumor‐suppressive roles of ΔNp63β and miR‐205 by inhibiting EMT thorough modulating ZEB1 and ZEB2 expression in OSCC.


  • 주제어

    ΔNp63β .   cancer .   EMT .   miRNA .   OSCC.  

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