Quantitative RNA-seq analysis of MITF dimer disruptor TT-012 treated B16F10 melanoma cells

Microphthalmia transcription factor, MITF, regulates normal melanocyte development and is the lineage specific survival oncogene of melanoma and clear cell sarcoma. MITF is essential for melanoma initiation, progression, and relapse and has been considered as an important therapeutic target. From a high throughput screening, we discovered the compound TT012, which binds to MITF and destroys the dimer formation and DNA binding ability of MITF. The impact of TT012 administration in B16F10 melanoma cells was further validated by RNA sequencing experiments. Using Ingenuity Pathway Analysis, MITF was identified as the second significantly inhibited transcription factor out of a total of 362 transcription factors. TBX2, a direct MITF target gene, which is a key developmental regulator of cell identity and an antisenescence factor in melanoma, was identified as the most significantly inhibited transcription factor. Together, these results demonstrated that TT012 treatment selectively inhibited the MITF mediated transcriptional network at a genome scale.