MicroRNA-18a promotes cancer progression through SMG1 suppression and mTOR pathway activation in nasopharyngeal carcinoma
| Autor: | Xiao Min Zhou, Rui Sun, Nuo Qing Weng, Hui Yun Wang, Ruo Wen Xiao, Te Yang, Rui Qi Wang, Mei Yin Zhang, Lu Shi, Xin Ge Zhao, Hai De Qin, Shi Juan Mai, Ji Liu |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Epstein-Barr Virus Infections Herpesvirus 4 Human Cancer Research Carcinogenesis Immunology Apoptosis Protein Serine-Threonine Kinases Biology Article Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Cell Line Tumor microRNA medicine Animals Humans Antagomir lcsh:QH573-671 Head and neck cancer PI3K/AKT/mTOR pathway Cell Proliferation Regulation of gene expression Nasopharyngeal Carcinoma lcsh:Cytology Cell growth TOR Serine-Threonine Kinases Cell Biology Middle Aged medicine.disease Gene Expression Regulation Neoplastic MicroRNAs Nasopharyngeal carcinoma chemistry miRNAs Disease Progression Cancer research Heterografts Female Ectopic expression Signal transduction Signal Transduction |
| Zdroj: | Cell Death and Disease, Vol 10, Iss 11, Pp 1-16 (2019) Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | miR-18a has been reported to be upregulated in nasopharyngeal carcinoma (NPC) tissues by microarray assays. However, the roles and the underlying mechanisms of miR-18a in NPC remain poorly understood. Here we demonstrated by real-time RT-PCR that miR-18a expression is upregulated in NPC tissues, and positively correlated with tumor size and TNM stage. Moreover, miR-18a expression could be upregulated by NF-κB activation or Epstein-Barr virus encoded latent membrane protein 1 expression. The ectopic expression of miR-18a promoted NPC cell proliferation, migration and invasion, while the repression of miR-18a had opposite effects. Candidate genes under regulation by miR-18a were screened out through a whole-genome microarray assay, further identified by a reporter assay and verified in clinical samples. SMG1, a member of the phosphoinositide 3-kinase-related kinases family and an mTOR antagonist, was identified as functional target of miR-18a. Our results confirmed that miR-18a exerts its oncogenic role through suppression of SMG1 and activation of mTOR pathway in NPC cells. Importantly, in vivo xenograft tumor growth in nude mice was effectively inhibited by intratumor injection of miR-18a antagomir. Our data support an oncogenic role of miR-18a through a novel miR-18a/SMG1/mTOR axis and suggest that the antitumor effects of antagomir-18a may make it suitable for NPC therapy. |
| Databáze: | OpenAIRE |
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