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

被引:33
|
作者
Sun, Hui [1 ]
Jiang, Pingdong [1 ]
机构
[1] Wuxi 2 Peoples Hosp, Dept Dermatol, Wuxi, Jiangsu, Peoples R China
来源
MOLECULAR GENETICS & GENOMIC MEDICINE | 2018年 / 6卷 / 06期
关键词
Basal cell carcinoma; K5tTA/TREGLI1; miRNA-451a; TBX1; TRANSCRIPTION FACTOR TBX1; DIAGNOSIS; MIR-451;
D O I
10.1002/mgg3.473
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:1001 / 1009
页数:9
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