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

Zhang J, Wang Y, Chen X, Zhou Y, Jiang F, Chen J, Wang L, Zhang WF - Oncotarget (2015)

Bottom Line: We demonstrated that the mRNA and protein levels of AREG were greatly reduced when forcing miR-34a expression.Moreover, the results of luciferase assay provided the further evidence that miR-34a degraded AREG mRNA through targeting the 3'-UTR site.Additionally, Over-expressing miR-34a greatly reduced EGFR and uPA, which were reversed by re-expression of AREG.

View Article: PubMed Central - PubMed

Affiliation: The 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.

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.

No MeSH data available.


Related in: MedlinePlus

miR-34a involves in ErbB pathway though suppressing AREG(A) 32 co-down-regulated mRNAs with log2 fold change ≤ –0.3, were subjected to KEGG pathway enrichment analysis. (B) Re-expression AREG reversed miR-34a induced EGFR and ErbB3 down-regulation in Fadu cell lines. (C) Re-expression AREG reversed miR-34a induced EGFR down-regulation in UM-SCC-23 cell lines.
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Figure 8: miR-34a involves in ErbB pathway though suppressing AREG(A) 32 co-down-regulated mRNAs with log2 fold change ≤ –0.3, were subjected to KEGG pathway enrichment analysis. (B) Re-expression AREG reversed miR-34a induced EGFR and ErbB3 down-regulation in Fadu cell lines. (C) Re-expression AREG reversed miR-34a induced EGFR down-regulation in UM-SCC-23 cell lines.

Mentions: The 32 co-down-regulated genes affected by forced miR-34a expression were performed by a KEGG pathway analysis. The result showed that the differentially regulated genes involved in P53 signaling pathway (p = 1.43E-05) and ErbB signaling pathway (p = 2.86E-05) were over-represented among the down-regulated mRNAs (log2 fold change ≤ –0.3, p < 0.01). Besides the well-known P53 signaling pathway, the influence of miR-34a in ErbB pathway is also important (Figure 8A).


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

Zhang J, Wang Y, Chen X, Zhou Y, Jiang F, Chen J, Wang L, Zhang WF - Oncotarget (2015)

miR-34a involves in ErbB pathway though suppressing AREG(A) 32 co-down-regulated mRNAs with log2 fold change ≤ –0.3, were subjected to KEGG pathway enrichment analysis. (B) Re-expression AREG reversed miR-34a induced EGFR and ErbB3 down-regulation in Fadu cell lines. (C) Re-expression AREG reversed miR-34a induced EGFR down-regulation in UM-SCC-23 cell lines.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480692&req=5

Figure 8: miR-34a involves in ErbB pathway though suppressing AREG(A) 32 co-down-regulated mRNAs with log2 fold change ≤ –0.3, were subjected to KEGG pathway enrichment analysis. (B) Re-expression AREG reversed miR-34a induced EGFR and ErbB3 down-regulation in Fadu cell lines. (C) Re-expression AREG reversed miR-34a induced EGFR down-regulation in UM-SCC-23 cell lines.
Mentions: The 32 co-down-regulated genes affected by forced miR-34a expression were performed by a KEGG pathway analysis. The result showed that the differentially regulated genes involved in P53 signaling pathway (p = 1.43E-05) and ErbB signaling pathway (p = 2.86E-05) were over-represented among the down-regulated mRNAs (log2 fold change ≤ –0.3, p < 0.01). Besides the well-known P53 signaling pathway, the influence of miR-34a in ErbB pathway is also important (Figure 8A).

Bottom Line: We demonstrated that the mRNA and protein levels of AREG were greatly reduced when forcing miR-34a expression.Moreover, the results of luciferase assay provided the further evidence that miR-34a degraded AREG mRNA through targeting the 3'-UTR site.Additionally, Over-expressing miR-34a greatly reduced EGFR and uPA, which were reversed by re-expression of AREG.

View Article: PubMed Central - PubMed

Affiliation: The 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.

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.

No MeSH data available.


Related in: MedlinePlus