TY - JOUR
T1 - Tumor-suppressive roles of ΔNp63β-miR-205 axis in epithelial–mesenchymal transition of oral squamous cell carcinoma via targeting ZEB1 and ZEB2
AU - Hashiguchi, Yuma
AU - Kawano, Shintaro
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
N1 - Funding Information:
This work was supported by a Grant-in-Aid (26463014, 16K21246, 26861729, 16K20584, 16H07063, 15K20539, 26670869) from the Japanese Ministry of Education, Culture, Sports, Science and Technology.
Publisher Copyright:
© 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.
PY - 2018/10
Y1 - 2018/10
N2 - 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.
AB - 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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U2 - 10.1002/jcp.26267
DO - 10.1002/jcp.26267
M3 - Article
C2 - 29150940
AN - SCOPUS:85046779987
SN - 0021-9541
VL - 233
SP - 6565
EP - 6577
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 10
ER -
