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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 suppressed the invasion of HNSCC cell lines in vitro(A) The cell invasion capability was dramatically reduced in the cells over-expressed miR-34a. (B) Ectopic miR-34a resulted fold decrease in HNSCC cells invasion (P < 0.01).
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Figure 2: MiR-34a suppressed the invasion of HNSCC cell lines in vitro(A) The cell invasion capability was dramatically reduced in the cells over-expressed miR-34a. (B) Ectopic miR-34a resulted fold decrease in HNSCC cells invasion (P < 0.01).

Mentions: To further elucidate the function of miR-34a in the metastatic process of HNSCC, four HNSCC cell lines (Fadu, SCC-15, UM-SCC-23, and Cal27) were stably over-expressed miR-34a using lentiviral vector. The miR-34a expression was enhanced dramatically in miR-34a transfected cells compared with the control (p < 0.01, Supplementary Figure 1). The ectopic miR-34a expression caused a significant reduction of cell invasion capability (Figure 2A). Statistically, over-expression of miR-34a resulted in 7.64-fold decrease in Fadu cell invasion, 2.23-fold decrease in SCC-15 invasion, 5.84-fold decrease in UM-SCC-23 invasion, and 2.81-fold decrease in Cal27, compared with the cells transfected with control vector (P < 0.01, Figure 2B).


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 suppressed the invasion of HNSCC cell lines in vitro(A) The cell invasion capability was dramatically reduced in the cells over-expressed miR-34a. (B) Ectopic miR-34a resulted fold decrease in HNSCC cells invasion (P < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: MiR-34a suppressed the invasion of HNSCC cell lines in vitro(A) The cell invasion capability was dramatically reduced in the cells over-expressed miR-34a. (B) Ectopic miR-34a resulted fold decrease in HNSCC cells invasion (P < 0.01).
Mentions: To further elucidate the function of miR-34a in the metastatic process of HNSCC, four HNSCC cell lines (Fadu, SCC-15, UM-SCC-23, and Cal27) were stably over-expressed miR-34a using lentiviral vector. The miR-34a expression was enhanced dramatically in miR-34a transfected cells compared with the control (p < 0.01, Supplementary Figure 1). The ectopic miR-34a expression caused a significant reduction of cell invasion capability (Figure 2A). Statistically, over-expression of miR-34a resulted in 7.64-fold decrease in Fadu cell invasion, 2.23-fold decrease in SCC-15 invasion, 5.84-fold decrease in UM-SCC-23 invasion, and 2.81-fold decrease in Cal27, compared with the cells transfected with control vector (P < 0.01, Figure 2B).

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