Exploring The Effect And Mechanism Of MacroH2A1 On The Proliferation,migration And Invasion Of Melanoma

Background: The number of melanoma incidence is increasing year to year.Worldwide,the number of new cases of cutaneous melanoma accounted for about 21% of all new cases of skin cancer in 2020,but the number of deaths accounted for 47% of all deaths from cutaneous malignancies.In recent years,melanoma immunotherapy and targeted therapy have made remarkable progress.However,melanoma is characterised by high aggressiveness,frequent recurrence,early metastasis and drug resistance,which are the challenges of melanoma cure.MacroH2A1,a variant of the core histone H2 A,is deficiently expressed in a variety of tumour tissues and cells,and its expression levels correlate with the proliferation,invasion and metastasis of a variety of tumours.It has been shown that MacroH2A1 expression is absent in melanoma tissues,suggesting that MacroH2A1 may play a key role in melanoma progression,however,its effects on proliferation,migration and invasion of human melanoma and the specific molecular mechanisms have not been fully elucidated.Objective: To explore the effect of MacroH2A1 on the proliferation,migration and invasion of melanoma and to explore its possible molecular mechanisms,it may offer new therapeutic targets for the treatment of melanoma.Methods: RT-qPCR and Western Blot were performed to detect the difference in expression of MacroH2A1 in human melanoma cells A375,SK-MEL-5,SK-MEL-28 and in human immortalized HaCaT keratinocytes.MACROH2A1 was knocked down/over-expressed in human melanoma cells A375,and the changes of cell proliferation capacity in vivo/in vitro were detected by EdU cell proliferation assay,plate clone formation assay and nude mouse xenograft tumor subcutaneous injection assay to detect changes in cell proliferation ability in vivo/in vitro.Transwell migration and invasion assay were used to exam the changes of cell migration and invasion after transfection.The altered expression of differential genes after transfection was detected by RT-qPCR and Western Blot assay.Results: By analyzing the expression levels of MacroH2A1 in human melanoma cells A375,SK-MEL-5,SK-MEL-28 and human immortalized HaCaT keratinocytes,it was found that MacroH2A1 expression was absent in human melanoma cells.Proliferation assays showed that MacroH2A1 was able to inhibit the proliferation of human melanoma cells in vitro and in vivo,and Transwell assays showed that MacroH2A1 was able to inhibit the migration and invasion of human melanoma cells.Knockdown/overexpression of MACROH2A1 and corresponding increase/decrease in SOX2 and MITF expression levels.Conclusion: MacroH2A1 is a novel prognostic indicator for melanoma.MacroH2A1 may inhibit the proliferation,migration and invasion of melanoma cells by inhibiting SOX2 and MITF.