Transcription factor YY1 contributes to human melanoma cell growth through modulating the p53 signalling pathway

Abstract

Melanoma has a higher mortality rate than any other skin cancer, and its cases are increasing. The transcription factor YY1 has been proven to be involved in tumour progression; however, the role of YY1 in melanoma is not well understood. This study investigates how YY1 functions in melanoma progression, and it also elucidates the underlying mechanisms involved. We have found that in clinical human melanoma tissues, YY1 is overexpressed compared with YY1 expression in normal melanocytes and skin tissues. Cellular immunofluorescence shows that YY1 is mainly located in the nucleus. YY1 knockdown reduces proliferation, migration and invasion of melanoma cell lines. Moreover, the apoptosis rate of cells is significantly increased in low-YY1 environments. The overexpression of YY1 resulted in decreased apoptotic rates in melanoma cells. YY1 also affects the expression of EMT-related proteins. Additional experiments reveal that YY1 knockdown disrupts the interaction of MDM2-p53, and that it both stabilizes and increases p53 activity. The upregulation of p53 expression in turn stimulates p21 expression just as it suppresses CDK4 expression, which then induces cells that were arrested in the G1 phase. The effect then is to constrain cell proliferation in melanoma cells. Upon activation of the p53 pathway, Bax, a pro-apoptotic protein, is upregulated, and Bcl-2, an anti-apoptotic protein, was downregulated in A375 cells. The findings of this study provide novel insights into the pathology of melanoma as well as the role that YY1 plays in tumour progression. The findings also suggest that targeting YY1 has the potential to improve the diagnosis and treatment of melanoma.