Emodin can dissociate NCOR2 from the promoter of SerRS. (A) Two classic retinoic acid response elements (RARE) motifs located on the promoter of SerRS (DR, direct repeats; X, any nucleotide; n, number of interspacing nucleotides). (B) Co-immunoprecipitation with anti-NCOR2, anti-RARα and anti-RXRα antibodies of cell lysates after 48 h treatment of MDA-MB-231 cells with DMSO or emodin (10 µM). (C) mRNA levels of SerRS, HOXB1, PCK1, and UCP1 from MDA-MB-231 cells treated with emodin (10 µM) relative to controls (n=3). (D-F) Chromatin Immunoprecipitation assays of MDA-MB-231 cells with, anti-RARα, anti-NCOR2 and anti-HDAC3 antibodies followed by qPCR with specific primers for the SerRS promoter (n=3; **p<0.01, ***p<0.001, ns, no significant difference; by Student's t-test). (G) Model for angiogenesis inhibition by emodin through direct targeting of NCOR2 and subsequent inactivation of the SerRS/VEGFA axis.
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