MiR-34a suppresses amphiregulin and tumor metastatic potential of head and neck squamous cell carcinoma (HNSCC)
| Autor: | Jiali Zhang, Li Wang, Jirong Chen, Yi Zhou, Fangyan Jiang, Yu Wang, Wen-Feng Zhang, Xinming Chen |
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| Rok vydání: | 2015 |
| Předmět: |
Oncology
Untranslated region EGF Family of Proteins medicine.medical_specialty Microarray Mice Nude Biology Amphiregulin Metastasis In vivo Cell Line Tumor Internal medicine microRNA medicine metastasis Animals Humans Neoplasm Metastasis Cell Proliferation Mice Inbred BALB C Squamous Cell Carcinoma of Head and Neck Cell growth Head and neck squamous cell carcinoma medicine.disease Head and neck squamous-cell carcinoma ErbB Receptors MicroRNAs stomatognathic diseases Head and Neck Neoplasms Carcinoma Squamous Cell Cancer research Female miR-34a Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | MiR-34a is a well-known tumor metastasis inhibitor, but only a few target genes involved in metastasis have been identified. In HNSCC, the role of miR-34a in metastasis has not been fully elaborated, and the target gene of miR-34a is still blind. Here we addressed that, the relative lower expression of miR-34a is associated with HNSCC lymphatic metastasis. HNSCC metastasis was found to be strongly suppressed in vitro and in vivo by over-expressing miR-34a. In order to screen the possible target genes of miR-34a in HNSCC, a microarray-based differential mRNA profiling mediated by miR-34a over-expression was performed, and AREG was identified as a pivotal target. We demonstrated that the mRNA and protein levels of AREG were greatly reduced when forcing miR-34a expression. The correlation between AREG mRNA levels and HNSCC metastatic phenotype was also significant in HNSCC tissues (p < 0.01). Moreover, the results of luciferase assay provided the further evidence that miR-34a degraded AREG mRNA through targeting the 3′-UTR site. Restoration of AREG expression partially rescued miR-34a-mediated cell invasion defects in vivo and in vitro. Additionally, Over-expressing miR-34a greatly reduced EGFR and uPA, which were reversed by re-expression of AREG. Taken together, these findings indicate that miR-34a targets AREG, and is essential in inhibition of HNSCC metastasis. |
| Databáze: | OpenAIRE |
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