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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

The expressions of miR-34a in HNSCC samples(A) The relative expressions of miR-34a in NHSCC tumors and the adjacent normal epithelial tissues. (M, lymph node metastatic samples; NM, non-metastatic samples). (B) The relative expressions of miR-34a in metastatic samples were significantly lower than that in non-metastatic samples.
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Figure 1: The expressions of miR-34a in HNSCC samples(A) The relative expressions of miR-34a in NHSCC tumors and the adjacent normal epithelial tissues. (M, lymph node metastatic samples; NM, non-metastatic samples). (B) The relative expressions of miR-34a in metastatic samples were significantly lower than that in non-metastatic samples.

Mentions: In order to evaluate the expression of miR-34a in HNSCC tissues, real-time RT-PCR was performed in the human fresh specimens obtained from 40 primary HNSCC tumors and the adjacent normal epithelial tissues. About 42.0-fold to 1.3-fold reduction of miR-34a expression was found in 29 of 40 (72.5%) HNSCC tissues, compared with the adjacent normal epithelia (Figure 1A).


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)

The expressions of miR-34a in HNSCC samples(A) The relative expressions of miR-34a in NHSCC tumors and the adjacent normal epithelial tissues. (M, lymph node metastatic samples; NM, non-metastatic samples). (B) The relative expressions of miR-34a in metastatic samples were significantly lower than that in non-metastatic samples.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: The expressions of miR-34a in HNSCC samples(A) The relative expressions of miR-34a in NHSCC tumors and the adjacent normal epithelial tissues. (M, lymph node metastatic samples; NM, non-metastatic samples). (B) The relative expressions of miR-34a in metastatic samples were significantly lower than that in non-metastatic samples.
Mentions: In order to evaluate the expression of miR-34a in HNSCC tissues, real-time RT-PCR was performed in the human fresh specimens obtained from 40 primary HNSCC tumors and the adjacent normal epithelial tissues. About 42.0-fold to 1.3-fold reduction of miR-34a expression was found in 29 of 40 (72.5%) HNSCC tissues, compared with the adjacent normal epithelia (Figure 1A).

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