AURKA Suppresses Leukemic THP-1 Cell Differentiation through Inhibition of the KDM6B Pathway

Molecules and Cells
Jin Woo ParkSang-Beom Seo

Abstract

Aberrations in histone modifications are being studied in mixed-lineage leukemia (MLL)-AF9-driven acute myeloid leukemia (AML). In this study, we focused on the regulation of the differentiation of the MLL-AF9 type AML cell line THP-1. We observed that, upon phorbol 12-myristate 13-acetate (PMA) treatment, THP-1 cells differentiated into monocytes by down-regulating Aurora kinase A (AURKA), resulting in a reduction in H3S10 phosphorylation. We revealed that the AURKA inhibitor alisertib accelerates the expression of the H3K27 demethylase KDM6B, thereby dissociating AURKA and YY1 from the KDM6B promoter region. Using Flow cytometry, we found that alisertib induces THP-1 differentiation into monocytes. Furthermore, we found that treatment with the KDM6B inhibitor GSK-J4 perturbed the PMA-mediated differentiation of THP-1 cells. Thus, we discovered the mechanism of AURKA-KDM6B signaling that controls the differentiation of THP-1 cells, which has implications for biotherapy for leukemia.

Citations

Nov 9, 2019·Protein & Cell·Xiangxian ZhangXiawei Wei
Jan 23, 2021·International Journal of Molecular Sciences·Anna SanchezDominique Bernard-Gallon
Jul 14, 2021·Molecules and Cells·Hyun Jeong KimSang-Beom Seo

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Methods Mentioned

BETA
immunoprecipitation
PMA
ChIP
PCR
co-immunoprecipitation
co-immunoprecipitation assay
histone acetylation
acetylation

Software Mentioned

PROMO
Excel

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