Interplay between ΔNp63 and miR-138-5p regulates growth, metastasis and stemness of oral squamous cell carcinoma
| Autor: | Xiaozhe Han, Zehang Zhuang, Pei Yu, Xiqiang Liu, Nan Xie, Hongzhang Huang, Cheng Wang, Xingxue Hu, Jinsong Hou, Jing Hu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pathology Apoptosis Metastasis Mice 0302 clinical medicine Cell Movement Tumor Cells Cultured miR-138 Mouth neoplasm Mice Inbred BALB C Middle Aged Prognosis Gene Expression Regulation Neoplastic Survival Rate oral squamous cell carcinoma Oncology Lymphatic Metastasis ΔNp63 030220 oncology & carcinogenesis Carcinoma Squamous Cell Neoplastic Stem Cells Oral and maxillofacial surgery Female Mouth Neoplasms Research Paper medicine.medical_specialty miR-138-5p Mice Nude stemness 03 medical and health sciences microRNA Oral and maxillofacial pathology Biomarkers Tumor medicine Carcinoma Animals Humans metastasis Cell Proliferation Neoplasm Staging Cell growth business.industry Tumor Suppressor Proteins medicine.disease Xenograft Model Antitumor Assays MicroRNAs stomatognathic diseases 030104 developmental biology Cancer research business Transcription Factors |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.15752 |
| Popis: | // Zehang Zhuang 1, 2 , Nan Xie 1, 3 , Jing Hu 1, 2 , Pei Yu 1, 2 , Cheng Wang 1, 2 , Xingxue Hu 4, 5 , Xiaozhe Han 4 , Jinsong Hou 1, 2 , Hongzhang Huang 1, 2 , Xiqiang Liu 1, 2 1 Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China 2 Department of Oral and Maxillofacial Surgery, Guanghua School and Hospital of Stomatology, Sun Yat-Sen University, Guangzhou, China 3 Department of Oral Pathology, Guanghua School and Hospital of Stomatology, Sun Yat-Sen University, Guangzhou, China 4 Department of Immunology and Infectious Disease, The Forsyth Institute, Cambridge, MA, USA 5 Division of General Practice and Materials Science, The Ohio State University College of Dentistry, Columbus, OH, USA Correspondence to: Hongzhang Huang, email: drhuang52@163.com Xiqiang Liu, email: liuxiq@mail.sysu.edu.cn Keywords: oral squamous cell carcinoma, ΔNp63, miR-138-5p, metastasis, stemness Received: October 29, 2016 Accepted: January 25, 2017 Published: February 27, 2017 ABSTRACT 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. |
| Databáze: | OpenAIRE |
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