Tumor-suppressive roles of ΔNp63β-miR-205 axis in epithelial-mesenchymal transition of oral squamous cell carcinoma via targeting ZEB1 and ZEB2.
Tumor-suppressive roles of ΔNp63β-miR-205 axis in epithelial-mesenchymal transition of oral squamous cell carcinoma via targeting ZEB1 and ZEB2.
复制标题
DOI：
10.1002/jcp.26267
复制
发表时间：
2018-10
影响因子：
5.6
通讯作者：
Nakamura S
中科院分区：
文献类型：
--
作者：
Hashiguchi Y;Kawano S;Goto Y;Yasuda K;Kaneko N;Sakamoto T;Matsubara R;Jinno T;Maruse Y;Tanaka H;Morioka M;Hattori T;Tanaka S;Kiyoshima T;Nakamura S
我们先前发现，在口腔鳞状细胞癌（OSCC）中，上皮向间质转化（EMT）由Δ Np 63 β（Δ Np 63的剪接变体）介导。最近的研究强调了microRNA（miRNA）参与癌细胞的EMT，尽管其机制尚不清楚。为了鉴定负责Δ Np 63 β介导的EMT的miRNA，通过在OSCC细胞中Δ Np 63 β过表达进行miRNA微阵列分析; SQUU-B，其缺乏Δ Np 63表达并显示EMT表型。miRNAs微阵列分析显示miR-205在Δ Np 63 β-过表达后上调最多。在OSCC细胞中，miR-205表达与Δ Np 63正相关，与miR-205的潜在靶点锌指E盒结合同源框（ZEB）1和ZEB 2负相关。通过miR-205模拟物转染到SQUU-B细胞中的miR-205过表达导致ZEB 1、ZEB 2和间充质标志物减少，上皮标志物增加，细胞运动性降低，表明EMT表型抑制。有趣的是，通过将miR-205抑制剂转染到表达Δ Np 63和miR-205的OSCC细胞中获得了与此现象相反的结果。此外，靶标保护剂分析显示miR-205直接调节ZEB 1和ZEB 2表达。这些结果表明Δ Np 63 β和miR-205通过抑制EMT，通过调节ZEB 1和ZEB 2在OSCC中的表达而发挥肿瘤抑制作用。
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.
登录
查看更多内容
影响因子：
6.2
作者：
Majid, Shahana;Dar, Altaf A.;Saini, Sharanjot;Yamamura, Soichiro;Hirata, Hiroshi;Tanaka, Yuichiro;Deng, Guoren;Dahiya, Rajvir
通讯作者：
Dahiya, Rajvir
DOI：
10.1186/1758-3284-2-9
发表时间：
2010-04-20
期刊：
Head & neck oncology
影响因子：
--
作者：
Jerjes W;Upile T;Petrie A;Riskalla A;Hamdoon Z;Vourvachis M;Karavidas K;Jay A;Sandison A;Thomas GJ;Kalavrezos N;Hopper C
通讯作者：
Hopper C
影响因子：
4.2
作者：
Kimura, Sotai;Naganuma, Seiji;Itoh, Hiroshi
通讯作者：
Itoh, Hiroshi
影响因子：
21.3
作者：
Batlle, E;Sancho, E;de Herreros, AG
通讯作者：
de Herreros, AG
影响因子：
1.6
作者：
Jin, Chenyu;Liang, Ruojia
通讯作者：
Liang, Ruojia