Interplay between ΔNp63 and miR-138-5p regulates growth, metastasis and stemness of oral squamous cell carcinoma.
Interplay between ΔNp63 and miR-138-5p regulates growth, metastasis and stemness of oral squamous cell carcinoma.
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Delta Np63 和 miR-138-5p 之间的相互作用调节口腔鳞状细胞癌的生长、转移和干性
DOI：
10.18632/oncotarget.15752
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发表时间：
2017-03-28
期刊：
影响因子：
--
通讯作者：
Liu X
中科院分区：
文献类型：
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作者：
Zhuang Z;Xie N;Hu J;Yu P;Wang C;Hu X;Han X;Hou J;Huang H;Liu X
TP 63在上皮细胞发育和各种癌症的进展中起主要调节剂的作用，但其在口腔癌发病机制中的作用仍然未知。本研究旨在探讨TP 63在口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）发生发展中的作用。本研究表明，TP 63的主要亚型Δ Np 63在口腔鳞癌组织和细胞系中的表达较正常组织和细胞系显著上调，其表达与口腔鳞癌的病理分化、淋巴结转移和临床分期密切相关。Δ Np 63的过表达促进了OSCC细胞的生长、转移和干细胞样特性，而Δ Np 63的缺失在体外和体内均显著抑制了OSCC细胞的表型。Δ Np 63亚型在转录上抑制miR-138- 5 p表达; miR-138- 5 p表达的恢复部分消除了上调Δ Np 63的作用。这项研究还表明，miR-138- 5 p直接靶向Δ Np 63，导致与Δ Np 63的串扰。Δ Np 63和miR-138- 5 p之间的相关性在OSCC组织中得到进一步验证，并被发现与OSCC患者的预后显著相关。因此，我们的数据显示Δ Np 63和miR-138- 5 p之间的相互作用通过调节细胞生长、转移和干性促进OSCC进展。
TP63 acts as a master regulator in epithelia development and in the progression of various cancers, but its role in oral cancer pathogenesis remains unknown. This study aimed to explore the role of TP63 in the progression of oral squamous cell carcinoma (OSCC). This study shows that ΔNp63, the predominant isoform of TP63, is significantly upregulated in OSCC tissues and cell lines compared with their normal counterparts, and its expression is closely correlated with pathological differentiation, lymph node metastasis and clinical stage in patients with OSCC. The overexpression of ΔNp63 promotes growth, metastasis and stem-like properties in OSCC cells, and ΔNp63 depletion significantly represses OSCC cellular phenotypes in vitro and in vivo. The ΔNp63 isoform transcriptionally suppresses miR-138-5p expression; restoration of miR-138-5p expression partially abolishes the effect of upregulating ΔNp63. This study also demonstrates that miR-138-5p directly targets ΔNp63, resulting in crosstalk with ΔNp63. The correlation between ΔNp63 and miR-138-5p was further validated in OSCC tissues and was found to be significantly associated with the prognosis of patients with OSCC. Therefore, our data reveal that the interplay between ΔNp63 and miR-138-5p promotes OSCC progression by regulating cell growth, metastasis and stemness.