A New Insight on Activation of Human Endogenous Retroviruses (HERVs) in Malignant Melanoma upon Exposure to CuSO4

Abstract

Human endogenous retroviruses (HERVs) are semi-conserved subtypes of long-terminal repeats containing retrotransposons that constitute approximately 8% of the genome. Under pathological conditions, the expression of HERVs is also affected by epigenetic modifications. The extent to which the activation of human endogenous retroviruses can be influenced upon exposure to copper remains to be evaluated. Thus, the present study was designed to evaluate the effects of CuSO₄ administration on the transcriptional activity of three HERV families (H, K, and W) in human malignant melanoma cells. For this purpose, following the determination of less cytotoxic concentrations of copper sulfate, the human skin malignant melanoma SK-MEL-37 cells were treated with 25, 50, and 75 μM CuSO₄ for 96 h. Then, mRNA expression of env gene of HERV-H, HERV-K, and HERV-W was evaluated by qPCR. According to the results, 96-h treatment of SK-MEL-37 cells with 75 μM CuSO₄ could significantly downregulate HERV-H evn expression (P < 0.05). Moreover, exposure of 25 μM copper significantly upregulated the expression of HERV-K env (P < 0.05). Regarding HERV-W env, the expression level increased significantly in all treated concentrations (P < 0.05). It seems that the expression change was decreased in both HERV-W and HERV-K by increasing doses. The study results demonstrated that copper exposure to melanoma cells might promote tumor growth by inducing HERVs and/or control tumor development by decreasing the activation of HERVs in defined levels of copper. According to the findings of this study, copper might exert a binary effect on malignant melanoma.

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