American Association for Cancer Research
00085472can171933-sup-185542_2_supp_4352152_kyk2hs.pdf (273.98 kB)

Figure S1 from miR-519d Promotes Melanoma Progression by Downregulating EphA4

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journal contribution
posted on 2023-03-31, 01:03 authored by Kuo-Tai Hua, Jin-Bong Hong, Yi-Shuan Sheen, Hsin-Yi Huang, Yi-Ling Huang, Jau-Shiuh Chen, Yi-Hua Liao

Suppl. Figure 1. Loss of E-cadherin expression in A2058 melanoma cells. MCF7 breast cancer cell line was used as a positive control.


Ministry of Science and Technology (MOST)



Increasing evidence suggests that there is a unique cell subpopulation in melanoma that can form nonadherent melanospheres in serum-free stem cell medium, mimicking aggressive malignancy. Using melanospheres as a model to investigate progression mechanisms, we found that miR-519d overexpression was sufficient to promote cell proliferation, migration, invasion, and adhesion in vitro and lung metastatic capability in vivo. The cell adhesion receptor EphA4 was determined to be a direct target of miR-519d. Forced expression of EphA4 reversed the effects of miR-519d overexpression, whereas silencing of EphA4 phenocopied the effect of miR-519d. Malignant progression phenotypes were also affected at the level of epithelial-to-mesenchymal transition and the ERK1/2 signaling pathway inversely affected by miR-519d or EphA4 expression. In clinical specimens of metastatic melanoma, we observed significant upregulation of miR-519d and downregulation of EphA4, in the latter case correlated inversely with overall survival. Taken together, our results suggest a significant functional role for miR-519d in determining EphA4 expression and melanoma progression.Significance: These results suggest a significant role for miR-519d in determining expression of a pivotal cell adhesion molecule that may impact risks of malignant progression in many cancers. Cancer Res; 78(1); 216–29. ©2017 AACR.

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