miR-20b regulates expression of proteinase-activated receptor-1 (PAR-1) thrombin receptor in melanoma cells

被引:35
作者
Saleiban, Amina [1 ]
Faxalv, Lars [1 ]
Claesson, Kjersti [1 ]
Jonsson, Jan-Ingvar [1 ]
Osman, Abdimajid [1 ,2 ]
机构
[1] Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, Div Microbiol & Mol Med, Linkoping, Sweden
[2] Cty Council Ostergotland, Linkoping, Sweden
关键词
melanoma; metastasis; proteinase-activated receptor-1; gene expression regulation; microRNAs; TISSUE FACTOR; MESSENGER-RNA; MICRORNA CLUSTER; TUMOR-CELLS; CANCER; TARGET; GENE; METASTASIS; IDENTIFICATION; COAGULATION;
D O I
10.1111/pcmr.12217
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The proteinase-activated receptor 1 (PAR-1) plays a central role in melanoma progression and its expression level is believed to correlate with the degree of cancer invasiveness. Here, we show that PAR-1 is post-transcriptionally regulated by miR-20b microRNA in human melanoma cells. PAR-1 was found to be expressed in metastatic melanoma cells but was barely detectable in primary melanoma. By transducing primary melanoma cells with a lentivirus containing a 3-UTR construct of PAR-1 mRNA, we could show that endogenous melanoma microRNAs interacted with PAR-1 3-UTR and silenced a fused luciferase reporter. Transfection of an inhibitor against miR-20b into primary melanoma cells reversed this process. Finally, transfection of miR-20b mimic into metastatic melanoma cells caused downregulation of the luciferase reporter. We conclude that miR-20b regulates expression of melanoma PAR-1 receptor, which may explain the differential expression of PAR-1 observed in human melanoma.
引用
收藏
页码:431 / 441
页数:11
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