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RNA-seq analysis of human multiple myeloma cell line RPMI 8226 after HDAC1 knockdown

ABSTRACT: Histone deacetylases (HDACs) have emerged as therapeutic targets in multiple myeloma (MM); however, the underlying roles of each class- or isoform-HDAC have not fully clarified. The present study delineates the effect of HDAC1 suppression or inhibition in MM cells. The RNA-seq analysis here revealed that HDAC1 suppression downregulated IRF4 and PIM2, which both play a crucial role in MM cell survival and proliferation. Mechanistically, HDAC1 inhibition dampens IRF4 transcription through histone hyperacetylation and hindrance of RNA polymerase II recruitment at IRF4 locus. PIM2 is transcriptionally under direct regulation by IRF4, thereby reducing PIM2 expression after HDAC1 inhibition. PIM2 is upregulated by the stimuli from bone marrow microenvironment including IL-6 independent of IRF4 regulation in MM cells. Although these stimuli reduce the cytotoxic effect of HDAC1 inhibition in MM cells, direct blockade of PIM2 overcomes the weak point of HDAC1 inhibition. The effect of the combination of class I HDAC inhibitors with PIM inhibitors is further confirmed in vivo mouse xenograft models. Our findings provoke clinical applications of class I HDAC inhibitors in combination with PIM inhibitors against MM.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193298 | GEO | 2022/09/21

REPOSITORIES: GEO

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