miR-519d Promotes Melanoma Progression by Downregulating EphA4

Cancer Research
Kuo-Tai HuaYi-Hua Liao

Abstract

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 expre...Continue Reading

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Citations

Feb 6, 2020·International Journal of Molecular Sciences·Francesca Varrone, Emilia Caputo
Oct 30, 2019·Bioscience, Biotechnology, and Biochemistry·Lishan Ma, Jin Li
May 11, 2018·Cancer Cell International·Jia-Xiang AnDong-Qiu Dai
Mar 21, 2021·Journal of Experimental & Clinical Cancer Research : CR·Wenkang LuanJinlong Wang
May 11, 2021·Frontiers in Oncology·Soudeh Ghafouri-FardMohammad Taheri
Jun 18, 2021·The Journal of Biological Chemistry·Taylor P LightElena B Pasquale
Sep 9, 2021·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·Pihong LiMingdong Lu

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