miR-488-3p sponged by circ-0000495 and mediated upregulation of TROP2 in head and neck squamous cell carcinoma development
| Autor: | Zeming Fu, Yingyuan Guo, Guofang Guan, Yanru Hao, Dejun Zhang, Duo-Jiao Yu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Gene knockdown microRNA circular RNA Biology head and neck squamous cell carcinoma medicine.disease Head and neck squamous-cell carcinoma Metastasis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology Downregulation and upregulation 030220 oncology & carcinogenesis medicine Cancer research Immunohistochemistry Protein kinase B TROP2 prognostic marker Research Paper |
| Zdroj: | Journal of Cancer |
| ISSN: | 1837-9664 |
| DOI: | 10.7150/jca.40339 |
| Popis: | TROP2 (trophoblast cell surface antigen 2) overexpression has been reported in many human cancers. The correlation between TROP2 and tumor aggressiveness has implied it could be a prognostic indicator. However, the roles of TROP2 and their underlying mechanisms remain of great interest in head and neck squamous cell carcinoma (HNSCC) biology. In the current study, the prognostic significance of TROP2 in HNSCC archival samples was determined using immunohistochemistry. Quantitative reverse transcriptase PCR (qRT-PCR) was used to measure the phenotypic effects of TROP2 knockdown, miR-488-3p re-expression, and circRNAs expression. Cell viability, migration/invasion as well as in vivo tumor formation assays were accessed. The interactions of miRNAs-TROP2 or circRNAs-miRNAs were determined by qRT-PCR, western blot analysis and luciferase assays. TROP2 was demonstrated overexpression in HNSCC patients and cancer cell lines. High expression of TROP2 was significantly associated with patient relapse. TROP2 promoted tumor cell proliferation, migration, invasion, and tumor growth, through AKT and MAPK pathways. Further investigation revealed that TROP2 is a direct target of miR-488-3p, while circ-0000495 bounds to miR-488-3p. Our study unraveled a novel mechanism by which down-regulation of miR-488-3p sponged by circ-0000495 releases its epigenetic silencing to TROP2. The increased TROP2 promotes tumor proliferation, therefore, providing evidence in support of targeting the circ-0000495/miR-488-3p/TROP2 axis in contributing to HNSCC therapy and preventing tumor metastasis. |
| Databáze: | OpenAIRE |
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