RNA-Seq analysis of the impact of a kinase NIK inhibitor (DMBP5) on the human melanoma cell line A375 (replicate 1)

Introduction: there is growing evidence that the IFN-γ-related cytokine signature plays a major role supporting the effect of pharmacological blockade of immune checkpoints. The expression of IFN-γ in cancer cells is repressed by several factors, among them a key role is played by the oncogene EZH2, which in turns is controlled by the non-canonical NF-kB pathway and its upstream kinase, NIK. Methodology: we developed a series of NIK inhibitors and compared the effects on cancer cells of one of them (DMBP5) to an siRNA against NIK via transcriptomic analysis (RNA-seq). Results: mRNA modifications induced by DMBP5 on A375 melanoma cells closely resemble the ones observed with siRNA against NIK. Conclusions: DMBP5 is a very selective and effective non-competitive NIK inhibitor (first in class). comparisons of mRNA changes at 2 time points (48 and 96 hrs) in a melanoma cell lines (A375) between DMBP5 (NIK small molecule inhibitor) and siRNA against NIK each of them normalized for their respective controls (DMSO or siRNA controls).