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Mol Genet Genomic Med. 2018 Nov;6(6):1001-1009. doi: 10.1002/mgg3.473. Epub 2018 Sep 13.

MicroRNA-451a acts as tumor suppressor in cutaneous basal cell carcinoma.

Author information

1
Department of Dermatology, Wuxi No.2 People's Hospital, Wuxi, Jiangsu, China.

Abstract

BACKGROUND:

Basal cell carcinoma (BCC) is the most common type of skin cancer. The underlying mechanism leading to BCC formation is not fully uncovered. The aim of this study was to characterize miRNA-451a as a novel tumor suppressor in cutaneous BCC.

METHODS:

We first evaluated miRNA-451a level in human BCC clinical tissues and inducible BCC mouse model. Then we studied the impact of overexpressing or inhibiting miR-451a in cell proliferation, colony formation potential, and cell cycle pattern. Next, we employed luciferase reporter assay and western blotting to evaluate TBX1 as a downstream target of miRNA-451a. Lastly, we confirmed TBX1 expressional change in BCC tissues by qPCR.

RESULTS:

miRNA-451a was significantly reduced in human BCC tissues. The downregulation of miRNA-451a was also confirmed in BCC mouse model. Overexpressing miRNA-451a in tumor cells markedly suppressed cell growth through G1 cell cycle arrest. However, inhibiting miRNA-451a in primary cells promoted cell growth and colony formation capacity. TBX1 (602054) was predicted as a downstream target of miRNA-451a and this was confirmed by luciferase assay and protein expression. Finally, TBX1 level was shown upregulated in BCC tissues as inversely to miR451a.

CONCLUSION:

Our studies revealed that miRNA-451a/TBX1 axis played a pivotal role in BCC tumorigenesis.

KEYWORDS:

TBX1 ; Basal cell carcinoma; K5tTA/TREGLI1; miRNA-451a

PMID:
30209892
PMCID:
PMC6305666
DOI:
10.1002/mgg3.473
[Indexed for MEDLINE]
Free PMC Article

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