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Abstract: )%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>apolipoprotein A-I (ApoA-I), the main protein component of high-density lipoprotein (HDL), plays a pivotal role in reverse cholesterol transport (RCT). Previous studies indicated a reduction of serum ApoA-I levels in various types of cancer, suggesting ApoA-I as a potential cancer biomarker. Herein, ectopically overexpressed ApoA-I in MDA-MB-231 breast cancer cells was observed to have antitumor effects, inhibiting cell proliferation and migration. Subsequent studies on the mechanism of expression regulation revealed that estradiol (E2)/estrogen receptor α; (ERα;) signaling activates ApoA-I gene transcription in breast cancer cells. Mechanistically, our ChIP-seq data showed that ERα directly binds to the estrogen response element (ERE) site within the ApoA-I gene and establishes an acetylation of histone 3 lysine 27 (H3K27ac)‍-enriched chromatin microenvironment. Conversely, Fulvestrant (ICI 182780) treatment blocked ERαbinding to ERE within the ApoA-I gene and downregulated the H3K27ac level on the ApoA-I gene. Treatment with p300 inhibitor also significantly decreased the ApoA-I messenger RNA (mRNA) level in MCF7 cells. Furthermore, the analysis of data from The Cancer Genome Atlas (TCGA) revealed a positive correlation between ERα and ApoA-I expression in breast cancer tissues. Taken together, our study not only revealed the antitumor potential of ApoA-I at the cellular level, but also found that ERα promotes the transcription of ApoA-I gene through direct genomic effects, and p300 may act as a co-activator of ERα in this process.

ERα通过在乳腺癌细胞中建立富含H3K27ac修饰的染色质微环境促进抑癌基因ApoA-I的转录

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