Selective molecular inhibition of the HDAC6 ZnF-UBP binding domain impairs multiple myeloma cell function

Histone deacetylase 6 (HDAC6) is overexpressed in multiple myeloma (MM) patients and may be involved in the acquisition of resistance to conventional treatments. To investigate the role of the HDAC6 ZnF-UBP domain in MM pathogenesis, we established two RPMI 8226 cell lines: one with a knock-out of HDAC6 (KO), and another one with a two-residue mutation in the HDAC6 ZnF-UBP domain (R1155A, Y1155A; RY) preventing its ubiquitin-binding capacity. Both cell lines were obtained by CRISPR-Cas9 edition. We then performed gene expression profiling analysis using data obtained by bulk RNA-seq of the three cell lines (RPMI 8226 WT, HDAC6 KO and HDAC6 RY).