MiR-34a suppresses amphiregulin and tumor metastatic potential of head and neck squamous cell carcinoma (HNSCC).

Abstract

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.

• Authors: Jiali Zhang, Yu Wang, Xinming Chen, Yi Zhou, Fangyan Jiang, Jirong Chen, Li Wang, Wen-Feng Zhang
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 10 Pg. 7454-69 (Apr 10 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25762634 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AREG protein, human
• Amphiregulin
• EGF Family of Proteins
• MIRN34 microRNA, human
• MicroRNAs
• EGFR protein, human
• ErbB Receptors

Topics

• Amphiregulin
• Animals
• Carcinoma, Squamous Cell (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (physiology)
• EGF Family of Proteins (genetics, metabolism)
• ErbB Receptors (antagonists & inhibitors, genetics, metabolism)
• Female
• Head and Neck Neoplasms (genetics, metabolism, pathology)
• Humans
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (biosynthesis, genetics)
• Neoplasm Metastasis
• Squamous Cell Carcinoma of Head and Neck