EZH1/2 Inhibition Augments the Anti-Tumor Effects of Sorafenib in Hepatocellular Carcinoma

Scientists investigated the relationship between the expression of EZH1/2 and the level of histone H3 Lysine 27 trimethylation in hepatocellular carcinoma.
[Scientific Reports]
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Targeting KDM6A Suppresses SREBP1c-Dependent Lipid Metabolism and Prostate Tumorigenesis

Scientists reported that specific homozygous deletion of KDM6A in the adult mouse prostate epithelium strongly inhibited tumor progression initiated by the homozygous loss of PTEN. Mechanistically, KDM6A promoted prostate tumorigenesis and lipid metabolism by binding to the SREBP1c promoter which resulted in increased SREBP1c transcription.
[Cancer Research]
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Loss of a 7q Gene, CUX1, Disrupts Epigenetically Driven DNA Repair and Drives Therapy-Related Myeloid Neoplasms

Scientists reported that CUX1 had a critical early role in the DNA repair process in hematopoietic stem and progenitor cells. Mechanistically, CUX1 recruited the histone methyltransferase EHMT2 to DNA breaks to promote downstream H3K9 and H3K27 methylation, phosphorylated ATM retention, subsequent γH2AX focus formation and propagation, and, ultimately, 53BP1 recruitment.
[Blood]
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Efficient Derivation of Human Trophoblast Stem Cells from Primed Pluripotent Stem Cells

Scientists reported the successful generation of trophoblast stem cells (TSCs) from primed human PSCs (hPSCs) and showed that BMP4 substantially enhanced this process. TSCs derived from primed hPSCs were similar to blastocyst-derived human TSCs in terms of morphology, proliferation, differentiation potential, and gene expression.
[Science Advances]
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Histone Deacetylase 2 Knockout Suppresses Immune Escape of Triple-Negative Breast Cancer Cells via Downregulating PD-L1 Expression

Scientists investigated the regulation of histone deacetylase 2 (HDAC2) on the interferon gamma-induced PD-L1 expression in TNBC cells and found the HDAC2 and PD-L1 expression in TNBC was significantly higher than that in non-TNBC, and HDAC2 was positively correlated with PD-L1 expression.
[Cell Death & Disease]
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Going beyond Polycomb: EZH2 Functions in Prostate Cancer

Scientists review how canonical functions of Enhancer of Zeste Homolog 2 as a histone methyltransferase activity are regulated and describe the various mechanisms of Polycomb Repressive Complex 2 recruitment to the chromatin.
[Oncogene]
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PCGF1 Promotes Epigenetic Activation of Stemness Markers and Colorectal Cancer Stem Cell Enrichment

Investigators identified PCGF1 as a crucial epigenetic regulator that sustained the stem cell-like phenotype of colorectal cancer (CRC). PCGF1 knockdown inhibited CRC stem cell proliferation and CRC stem cell enrichment.
[Cell Death & Disease]
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CBP/p300 HAT Maintains the Gene Network Critical for β Cell Identity and Functional Maturity

RNA-sequencing analysis showed a comprehensive downregulation of β cell and α cell identity genes in A-485-treated islets, without upregulation of dedifferentiation markers and derepression of disallowed genes.
[Cell Death & Disease]
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C646 Inhibits G2/M Cell Cycle-Related Proteins and Potentiates Anti-Tumor Effects in Pancreatic Cancer

Investigators found that the histone acetyltransferases inhibitor C646 augmented anti-tumor effects in vitro by inhibiting cell proliferation and cell cycle progression concomitantly with suppression of acetylated H3K9 and H3K27 expression.
[Scientific Reports]
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STAG2 Mutations Alter CTCF-Anchored Loop Extrusion, Reduce Cis-Regulatory Interactions and EWSR1-FLI1 Activity in Ewing Sarcoma

Using isogenic Ewing cells, researchers showed STAG2 loss of function profoundly changed the transcriptome but it did not significantly impact EWSR1-FLI1, CTCF/cohesin, or acetylated H3K27 DNA binding patterns.
[Cancer Cell]
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A Selective HDAC8 Inhibitor Potentiates Antitumor Immunity and Efficacy of Immune Checkpoint Blockade in Hepatocellular Carcinoma

The authors demonstrated that selective HDAC8 inhibition elicited effective and durable responses to immune-checkpoint blockade by co-opting adaptive immunity through enhancer reprogramming.
[Science Translational Medicine]
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