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Supplementary Tables S1-S2, Figures S1-S4 from Histone Methyltransferase hSETD1A Is a Novel Regulator of Metastasis in Breast Cancer

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posted on 2023-04-03, 17:42 authored by Tal Salz, Changwang Deng, Christine Pampo, Dietmar Siemann, Yi Qiu, Kevin Brown, Suming Huang

Supplementary Tables S1-S2, Figures S1-S4. Table S1. RT-PCR Primer Sequence Table S2. ChIP Primer Sequence Figure S1. Expression of TrxG in breast cancer samples. S2. hSETD1A Knockdown in MDA-MB-231 using independent shRNA constructs. S3. hSETD1A mRNA level predicts clinical outcomes for lymph-node positive breast cancer patients. S4. H3K4me3 and hSETD1A are correspondingly enriched at MMP promoters in breast cancer cells compared to epithelial breast cells.

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ARTICLE ABSTRACT

Epigenetic alteration is a hallmark of all cancers. Such alterations lead to modulation of fundamental cancer-related functions, such as proliferation, migration, and invasion. In particular, methylation of Histone H3 Lysine 4 (H3K4), a histone mark generally associated with transcriptional activation, is altered during progression of several human cancers. While the depletion of H3K4 demethylases promotes breast cancer metastasis, the effect of H3K4 methyltransferases on metastasis is not clear. Nevertheless, gene duplications in the human SETD1A (hSETD1A) H3K4 methyltransferase are present in almost half of breast cancers. Herein, expression analysis determined that hSETD1A is upregulated in multiple metastatic human breast cancer cell lines and clinical tumor specimens. Ablation of hSETD1A in breast cancer cells led to a decrease in migration and invasion in vitro and to a decrease in metastasis in nude mice. Furthermore, a group of matrix metalloproteinases (including MMP2, MMP9, MMP12, MMP13, and MMP17) were identified which were downregulated upon depletion of hSETD1A and demonstrated a decrease in H3K4me3 at their proximal promoters based on chromatin immunoprecipitation analysis. These results provide evidence for a functional and mechanistic link among hSETD1A, MMPs, and metastasis in breast cancer, thereby supporting an oncogenic role for hSETD1A in cancer.Implications: This study reveals that hSETD1A controls tumor metastasis by activating MMP expression and provides an epigenetic link among hSETD1A, MMPs, and metastasis of breast cancer. Mol Cancer Res; 13(3); 461–9. ©2014 AACR.

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