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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

(A) The relative expression of AREG mRNA in NHSCC tumors and the adjacent normal epithelial tissues(B) The relative expression of AREG mRNA in metastatic samples was significantly higher than that in non-metastatic samples. (C) General correlation between miR-34a and AREG mRNA relative expression in 40 samples. (D) The inverse correlation between miR-34a and AREG mRNA relative expression in 29 samples.
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Figure 10: (A) The relative expression of AREG mRNA in NHSCC tumors and the adjacent normal epithelial tissues(B) The relative expression of AREG mRNA in metastatic samples was significantly higher than that in non-metastatic samples. (C) General correlation between miR-34a and AREG mRNA relative expression in 40 samples. (D) The inverse correlation between miR-34a and AREG mRNA relative expression in 29 samples.

Mentions: To investigate whether AREG expression was inversely correlated with miR-34a in HNSCC tissues, the mRNA expression of AREG was evaluated by real-time RT-PCR in the 40 primary HNSCC tumors and the corresponding adjacent normal epithelial tissues. There were 29 of 40 (72.5%) HNSCC samples showed opposite expression trend between AREG and miR-34a (Figure 10A). Statistically, the relative AREG expression was negatively correlated with miR-34a in the 29 samples (Figure 10B, P = 0.0132), although general inverse correlation between miR-34a and AREG expression in all 40 tumor tissues was not observed (Figure 10C, P = 0.0745).


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)

(A) The relative expression of AREG mRNA in NHSCC tumors and the adjacent normal epithelial tissues(B) The relative expression of AREG mRNA in metastatic samples was significantly higher than that in non-metastatic samples. (C) General correlation between miR-34a and AREG mRNA relative expression in 40 samples. (D) The inverse correlation between miR-34a and AREG mRNA relative expression in 29 samples.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 10: (A) The relative expression of AREG mRNA in NHSCC tumors and the adjacent normal epithelial tissues(B) The relative expression of AREG mRNA in metastatic samples was significantly higher than that in non-metastatic samples. (C) General correlation between miR-34a and AREG mRNA relative expression in 40 samples. (D) The inverse correlation between miR-34a and AREG mRNA relative expression in 29 samples.
Mentions: To investigate whether AREG expression was inversely correlated with miR-34a in HNSCC tissues, the mRNA expression of AREG was evaluated by real-time RT-PCR in the 40 primary HNSCC tumors and the corresponding adjacent normal epithelial tissues. There were 29 of 40 (72.5%) HNSCC samples showed opposite expression trend between AREG and miR-34a (Figure 10A). Statistically, the relative AREG expression was negatively correlated with miR-34a in the 29 samples (Figure 10B, P = 0.0132), although general inverse correlation between miR-34a and AREG expression in all 40 tumor tissues was not observed (Figure 10C, P = 0.0745).

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