Interplay between ΔNp63 and miR-138-5p regulates growth, metastasis and stemness of oral squamous cell carcinoma
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Zehang Zhuang1,2, Nan Xie1,3, Jing Hu1,2, Pei Yu1,2, Cheng Wang1,2, Xingxue Hu4,5, Xiaozhe Han4, Jinsong Hou1,2, Hongzhang Huang1,2, Xiqiang Liu1,2
1Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China
2Department of Oral and Maxillofacial Surgery, Guanghua School and Hospital of Stomatology, Sun Yat-Sen University, Guangzhou, China
3Department of Oral Pathology, Guanghua School and Hospital of Stomatology, Sun Yat-Sen University, Guangzhou, China
4Department of Immunology and Infectious Disease, The Forsyth Institute, Cambridge, MA, USA
5Division of General Practice and Materials Science, The Ohio State University College of Dentistry, Columbus, OH, USA
Hongzhang Huang, email: [email protected]
Xiqiang Liu, email: [email protected]
Keywords: oral squamous cell carcinoma, ΔNp63, miR-138-5p, metastasis, stemness
Received: October 29, 2016 Accepted: January 25, 2017 Published: February 27, 2017
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.
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