机构：[1]State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No. 14, Sec. 3, Renminnan Road, Chengdu, Sichuan 610041, China[2]Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China四川省人民医院四川省肿瘤医院[3]Department of Stomatology, Zhoushan Hospital, Wenzhou Medical University. No .739, Dingshen Road, Lincheng Street, Zhoushan, 316021, Zhejiang,China[4]Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan 430068, China[5]State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Oral Pathology, West China Hospital of Stomatology, Sichuan University, No. 14, Sec. 3, Renminnan Road, Chengdu, Sichuan 610041, China
BACKGROUND: Dormancy is one characteristic of cancer cells to make patients remain asymptomatic before metastasis and relapse, which is closely related to the survival rate of cancer patients, including head and neck squamous cell carcinoma (HNSCC). PRRX1 has previously been implicated in the invasion and metastasis of the epithelial-mesenchymal transition (EMT) process in different types of human carcinoma. However, whether PRRX1 can regulate cancer dormancy and its reactivation, leading to the migration and invasion of HNSCC cells, remains elusive. The aim of this study was to determine the role of PRRX1 in cellular phenotype plasticity and cancer dormancy of HNSCC cells and its association with miRNAs in HNSCC. METHODS: The expression of PRRX1 was detected by immunohistochemical staining in primary HNSCC samples and the metastatic lymph nodes. Meanwhile, the role of PRRX1 and its relationship with miR-642b-3p and EMT in cellular phenotype plasticity and cancer dormancy of HNSCC were investigated in vitro and in vivo. RESULTS: PRRX1 was significantly higher at the invasive front of HNSCC samples compared with the metastatic lymph nodes, and such switch process was accompanied by the cellular phenotype plasticity and cell dormancy activation. In HNSCC cell lines, PRRX1 positively promoted the expression of known EMT inducers and cooperated with activated TGF-beta 1 to contribute to EMT and migration and invasion of HNSCC cells. Then, we found that overexpression of miR-642b-3p, one of the most significantly downregulated miRNAs in PRRX1-overexpressed cells, significantly reduced the migration and invasion, and increased cell proliferation and apoptosis. And miR-642b-3p restoration reversed PRRX1-induced cell dormancy and EMT of HNSCC cells through TGF-beta 2 and p38. Finally, we demonstrated that overexpressed PRRX1 was closely correlated with miR-642b-3p downregulation and the upregulation of TGF-beta 2 and p38 in a xenograft model of HNSCC. CONCLUSIONS: Our findings showed that PRRX1 may be one of the main driving forces for the cellular phenotype plasticity and tumor dormancy of HNSCC. Therefore, we can raise the possibility that EMT may help to keep cancer cell in dormant state and mesenchymal-epithelial transition may resurge dormancy in HNSCC.
基金：
National Natural Science Foundation
of China grants (Nos. 81672672, 81502357, 81572650, 81772891 and 81372891), by
National Program on Key Research Project of China (2016YFC0902700), by Natural
Science Foundation of Zhejiang Province (Q142114001), and by the Fundamental
Research Funds for the Central Universities (2017).
第一作者机构：[1]State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No. 14, Sec. 3, Renminnan Road, Chengdu, Sichuan 610041, China[2]Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
共同第一作者：
通讯作者：
通讯机构：[1]State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No. 14, Sec. 3, Renminnan Road, Chengdu, Sichuan 610041, China[5]State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Oral Pathology, West China Hospital of Stomatology, Sichuan University, No. 14, Sec. 3, Renminnan Road, Chengdu, Sichuan 610041, China[*1]State Key Laboratory of Oral Diseases&National Clinical Research Center forOral Diseases&Dept. of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No.14, Sec. 3, Renminnan Road, Chengdu, Sichuan 610041, China
推荐引用方式(GB/T 7714)：
Jian Jiang,Min Zheng,Mei Zhang,et al.PRRX1 Regulates Cellular Phenotype Plasticity and Dormancy of Head and Neck Squamous Cell Carcinoma Through miR-642b-3p[J].NEOPLASIA.2019,21(2):216-229.doi:10.1016/j.neo.2018.12.001.
APA：
Jian Jiang,Min Zheng,Mei Zhang,Xiao Yang,Li Li...&Xin-hua Liang.(2019).PRRX1 Regulates Cellular Phenotype Plasticity and Dormancy of Head and Neck Squamous Cell Carcinoma Through miR-642b-3p.NEOPLASIA,21,(2)
MLA：
Jian Jiang,et al."PRRX1 Regulates Cellular Phenotype Plasticity and Dormancy of Head and Neck Squamous Cell Carcinoma Through miR-642b-3p".NEOPLASIA 21..2(2019):216-229
