p54nrb is a new regulator of progression of malignant melanoma.

Nuclear RNA-binding protein p54nrb and its murine homolog NonO are known to be involved in a variety of nuclear processes including transcription and RNA processing. Melanoma inhibitory activity (MIA) has been shown to play an essential role in the progression of malignant melanoma and to influence melanomaassociated molecules and pathways in the early tumor formation steps. Interestingly, recent studies suggest that MIA is a regulator of p54nrb. Here, we show that p54nrb is strongly expressed and localized in the nucleus of both melanoma cell lines and melanoma tissue samples compared with normal human melanocytes or normal skin, respectively. Furthermore, all tested melanoma cell lines revealed strong p54nrb promoter activity. Treatment with MIAspecific small interfering RNAs showed an influence of MIA on p54nrb expression on both messenger RNA (mRNA) and protein level. Knockdown of p54nrb protein in melanoma cell lines led to reduced proliferation rates and to a strong decrease in their migratory potential. In addition, attachment to laminin and poly-Llysine was significantly increased. We could identify Connexin-43 (Cx-43) as a downstream target molecule of p54nrb as knockdown of p54nrb resulted in enhanced Cx-43 mRNA and protein levels. As a confirmation of these findings, melanoma cell lines showed very low Cx-43 expression levels compared with melanocytes. Our results demonstrate that p54nrb is highly expressed in malignant melanoma and, as a MIA target molecule, it seems to be involved in the development and progression of malignant melanoma.