摘要：Melanoma is one of the most aggressive types of cancer wherein resistance to treatment prevails. Therefore, it is important to discover novel molecular targets of melanoma progression as potential treatments. Here we show that paired-like homeodomain transcription factor 1 (
PITX1) plays a crucial role in the inhibition of melanoma progression through regulation of SRY-box transcription factors (
SOX) gene family mRNA transcription. Overexpression of
PITX1 in melanoma cell lines resulted in a reduction in cell proliferation and an increase in apoptosis. Additionally, analysis of protein levels revealed an antagonistic cross-regulation between SOX9 and SOX10. Interestingly, PITX1 binds to the
SOX9 promoter region as a positive regulatory transcription factor;
PITX1 mRNA expression levels were positively correlated with
SOX9 expression, and negatively correlated with
SOX10 expression in melanoma tissues. Furthermore, transcription of the long noncoding RNA (lncRNA), survival-associated mitochondrial melanoma-specific oncogenic noncoding RNA (
SAMMSON), was decreased in
PITX1-overexpressing cells. Taken together, the findings in this study indicate that
PITX1 may act as a negative regulatory factor in the development and progression of melanoma via direct targeting of the
SOX signaling.
