Down-regulated HDAC3 elevates microRNA-495-3p to restrain epithelial-mesenchymal transition and oncogenicity of melanoma cells via reducing TRAF5.

Yanbo Ma, Jincheng Duan, Xiuyan Hao

Journal of cellular and molecular medicine 2020 Nov

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MicroRNAs (miRNAs) are emerging biomarkers in biological processes and the role of miR-495-3p has been identified in melanoma, while the detailed molecular mechanisms remain to be further explored. We aim to explore the effect of histone deacetylase 3 (HDAC3) and miR-495-3p on epithelial-mesenchymal transition (EMT) and oncogenicity of melanoma cells by regulating tumour necrosis factor receptor-associated factor 5 (TRAF5). Levels of HDAC3, miR-495-3p and TRAF5 in melanoma tissues and pigmented nevus tissues were determined, and the predictive roles of HDAC3 and miR-495-3p in prognosis of melanoma patients were measured. The melanoma cells were screened and transfected with relative oligonucleotides and plasmids, and the expression of HDAC3, miR-495-3p and TRAF5, and phenotypes of melanoma cells were gauged by a series of assays. The relations between HDAC3 and miR-495-3p, and between miR-495-3p and TRAF5 were confirmed. HDAC3 and TRAF5 were increased while miR-495-3p was decreased in melanoma cells and tissues, and the low expression of miR-495-3p as well as high expression of HDAC3 indicated a poor prognosis of melanoma patients. Inhibited HDAC3 elevated miR-495-3p to suppress EMT and oncogenicity of melanoma cells by reducing TRAF5. HDAC3 particularly bound to miR-495-3p and TRAF5 was the target gene of miR-495-3p. Our results revealed that down-regulated HDAC3 elevates miR-495-3p to suppress malignant phenotypes of melanoma cells by inhibiting TRAF5, thereby repressing EMT progression of melanoma cells. This study may provide novel targets for melanoma treatment. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Citation

Yanbo Ma, Jincheng Duan, Xiuyan Hao. Down-regulated HDAC3 elevates microRNA-495-3p to restrain epithelial-mesenchymal transition and oncogenicity of melanoma cells via reducing TRAF5. Journal of cellular and molecular medicine. 2020 Nov;24(22):12933-12944