Research Papers:

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

Jiali Zhang _, Yu Wang, Xinming Chen, Yi Zhou, Fangyan Jiang, Jirong Chen, Li Wang and Wen-Feng Zhang

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Oncotarget. 2015; 6:7454-7469. https://doi.org/10.18632/oncotarget.3148

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Jiali Zhang1,2,*, Yu Wang1,2*, Xinming Chen1,2, Yi Zhou1, Fangyan Jiang1, Jirong Chen1, Li Wang1, Wen-Feng Zhang1

1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei_MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China

2Oral Histopathology Department, School and Hospital of Stomatology, Wuhan University, Wuhan, China

*These authors have contributed equally to this work

Correspondence to:

Jiali Zhang, e-mail: [email protected]

Xinming Chen, e-mail: [email protected]

Wen-Feng Zhang, e-mail: [email protected]

Keywords: Head and neck squamous cell carcinoma, miR-34a, amphiregulin, metastasis

Received: August 11, 2014     Accepted: January 16, 2015     Published: February 05, 2015


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.

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