Aurora kinase A phosphorylates histone methyltransferase NSD2 to promote drug resistance in multiple myeloma [RNA-Seq]

The epigenetic plasticity, such as DNA methylation and histone modification, has been suggested to be a potential mechanism controlling MM progression and drug resistance, but the underlying mechanisms are not fully understood. Here we demonstrate that some drug resistant genes were activated during myeloma resistance to bortezomib. Mechanistically, Aurora A can interact with NSD2, whose SET domain is responsible to H3K36me2 to enhance the transcriptional activity of Aurora A target gene. Once Aurora A is knocked out, H3K36me2 activity will change, changing the transcription activity of those drug resistant genes. LP-1 was infected by virus packging sgRNA targeting AURKA gene (Aurora A-KO) while the non-target control (NT Ctrl) was defined as control. Cells were harvested for gene expression profiling when AURKA was knocked out. Three replicates were performed.