As the principal active ingredient in the Chinese herb Tripterygium wilfordii Hook.F
(TwHF), triptolide has been shown to have very strong antitumor properties. The trimethylation of lysine
4 on histone H3 (H3K4me3) has been proposed to promote gene expression, and the accumulation
of H3K4me3 at the transcriptional start sites of oncogenes is involved in carcinogenesis. To identify
the association between the reduction of H3K4me3 and the apoptosis of MM cells induced by triptolide, we investigated
the global patterns of H3K4me3 occupancy in the MM cell genome. Combined analyses using ChIP-on-chip and western
blotting showed that H3K4me3 were highly enriched on the gene promoters of c-Myc and VEGFA and were associated
with the up-regulation of both genes. Treatment of KM3 cells with triptolide and siRNA targeting ASH2L reduced the expression
of c-Myc and VEGFA. These results suggest that triptolide can down-regulate c-Myc and VEGFA expression by
blocking the accumulation of H3K4me3 on their promoters,and thus play an important role in anti-MM mechanism.
Keywords: Apoptosis, ASH2L, c-Myc, H3K4me3, Multiple myeloma, Triptolide, VEGFA.
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