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

Yuma Hashiguchi, Shintarou Kawano, Yuichi Goto, Kaori Yasuda, Naoki Kaneko, Taiki Sakamoto, Ryota Matsubara, Teppei Jinno, Yasuyuki Maruse, Hideaki Tanaka, Masahiko Morioka, Taichi Hattori, Shoichi Tanaka, Tamotsu Kiyoshima, Seiji Nakamura

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6565-6577
Number of pages13
JournalJournal of cellular physiology
Volume233
Issue number10
DOIs
Publication statusPublished - Oct 1 2018

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Epithelial-Mesenchymal Transition
Tumors
Squamous Cell Carcinoma
MicroRNAs
Neoplasms
Microarrays
Microarray Analysis
Transfection
Cells
Phenotype
Zinc
Cell Movement
Epithelial Cells
B-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Tumor-suppressive roles of ΔNp63β-miR-205 axis in epithelial–mesenchymal transition of oral squamous cell carcinoma via targeting ZEB1 and ZEB2. / Hashiguchi, Yuma; Kawano, Shintarou; Goto, Yuichi; Yasuda, Kaori; Kaneko, Naoki; Sakamoto, Taiki; Matsubara, Ryota; Jinno, Teppei; Maruse, Yasuyuki; Tanaka, Hideaki; Morioka, Masahiko; Hattori, Taichi; Tanaka, Shoichi; Kiyoshima, Tamotsu; Nakamura, Seiji.

In: Journal of cellular physiology, Vol. 233, No. 10, 01.10.2018, p. 6565-6577.

Research output: Contribution to journalArticle

Hashiguchi, Yuma ; Kawano, Shintarou ; Goto, Yuichi ; Yasuda, Kaori ; Kaneko, Naoki ; Sakamoto, Taiki ; Matsubara, Ryota ; Jinno, Teppei ; Maruse, Yasuyuki ; Tanaka, Hideaki ; Morioka, Masahiko ; Hattori, Taichi ; Tanaka, Shoichi ; Kiyoshima, Tamotsu ; Nakamura, Seiji. / Tumor-suppressive roles of ΔNp63β-miR-205 axis in epithelial–mesenchymal transition of oral squamous cell carcinoma via targeting ZEB1 and ZEB2. In: Journal of cellular physiology. 2018 ; Vol. 233, No. 10. pp. 6565-6577.
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abstract = "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.",
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AU - Hashiguchi, Yuma

AU - Kawano, Shintarou

AU - Goto, Yuichi

AU - Yasuda, Kaori

AU - Kaneko, Naoki

AU - Sakamoto, Taiki

AU - Matsubara, Ryota

AU - Jinno, Teppei

AU - Maruse, Yasuyuki

AU - Tanaka, Hideaki

AU - Morioka, Masahiko

AU - Hattori, Taichi

AU - Tanaka, Shoichi

AU - Kiyoshima, Tamotsu

AU - Nakamura, Seiji

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