Conflict of interest: the authors declare that they have no conflicts of interest.
Experimental dermatology ● Original article
MLK3 promotes melanoma proliferation and invasion and is a target of microRNA-125b
Article first published online: 18 MAR 2014
© 2014 British Association of Dermatologists
Clinical and Experimental Dermatology
Volume 39, Issue 3, pages 376–384, April 2014
How to Cite
Zhang, J., Lu, L., Xiong, Y., Qin, W., Zhang, Y., Qian, Y., Jiang, H. and Liu, W. (2014), MLK3 promotes melanoma proliferation and invasion and is a target of microRNA-125b. Clinical and Experimental Dermatology, 39: 376–384. doi: 10.1111/ced.12286
The first three authors contributed equally to this work, and should be considered joint first authors.
- Issue published online: 18 MAR 2014
- Article first published online: 18 MAR 2014
- Manuscript Accepted: 18 SEP 2013
- National Natural Science Foundation of China. Grant Numbers: 31271264, 81100950
Metastatic melanoma is a disease with high mortality and limited therapeutic options. MicroRNAs (miRNAs) can be used to classify melanoma stage.
Expression of the miRNA miR-125b and serine/threonine kinase mixed lineage kinase (MLK)3 was assessed in primary malignant melanoma tissues and several melanoma cell lines by quantitative reverse transcription PCR. The effect of MLK3 and miR-125b on cell proliferation was evaluated by MTS assay, and cell invasion was evaluated by Transwell invasion assays. Targeting of MLK3 by miR-125b was evaluated using luciferase reporter assay and western blotting.
We found significantly increased levels of MLK3 in metastatic primary malignant melanomas and melanoma cell lines, with levels being especially high in metastatic lines. To investigate the functional significance of MLK3, we used knockdown MLK3, which was found to suppress cell growth and invasion. Using bioinformatics, we identified MLK3 as one potential target of miR-125b. miRNA transfection and luciferase assay confirmed that MLK3 was regulated by miR-125b at both the transcriptional and translational levels. Cell proliferation and cell invasion was inhibited by overexpression of miR-125b.
MLK3 is upregulated in metastatic melanoma, and regulates cell proliferation and invasion in melanoma cells. MLK3 is a direct target of miR-125b.