SETDB1 (SET Domain Bifurcated Histone Lysine Methyltransferase 1)

Both cytosolic RNA and DNA sensors were required for the ensuing interferon response and for the heightened sensitivity to PD-1 blockade elicited by ARID1A deficiency. These findings thus reveal an unanticipated heterochromatin gatekeeper function of ARID1A that operates outside the SWI/SNF complex and can be exploited to potentiate immune checkpoint therapy activity.

TIF1β-mediated epigenetic plasticity was recently shown to establish a leukemic chromatin environment for promoting oncogenic transcriptional programs while repressing lineage-differentiation regulators, which drives leukemic progression in a context-dependent manner. This review summarizes the dual role of TIF1β as a chromatin modulator, functioning both as a canonical transcriptional co-repressor and as a context-dependent co-activator, and also discusses how these modalities cooperate to sustain leukemic stem cell programs.

Luteolin may suppresses the viability, invasion, migration, and adhesion of lung cancer cells via co-treatment with mithramycin A.

Conclusion The TCGA-BRCA cohort analysis emphasizes a potential interplay of metabolic genes like NDUFS1, TRPM4, ARMCX5, SLCO6A1, and epigenetic axis genes like SETDB1 and USP37 in the oncogenesis and prognosis of breast carcinomas. These observations could open potential avenues for exploring novel therapeutics in aggressive breast carcinomas.

This aptamer was conjugated to the nucleolin-targeting aptamer AS1411, generating a single-strand PROTAC (AP-SETDB1-S6A) and a partial double-strand PROTAC (AP-SETDB1-D2), both of which exhibit good serum stability...Functional assays demonstrated that both AP-SETDB1-S6A and AP-SETDB1-D2 significantly inhibit breast cancer cell proliferation and migration, and resensitize drug-resistant breast cancer cells to tamoxifen. Notably, they further enhance the cytotoxic activity of CD8+ T cells against breast cancer cells and directly target breast cancer cells to suppress tumor growth in vivo. This study establishes dual aptamers-based PROTACs targeting SETDB1, offering effective therapeutic strategies for breast cancer treatment.

Notably, CHAMP1 deficiency induces synthetic lethality with FANCM inhibition in ALT-positive tumor cells, and the CHAMP1 complex is essential for the survival of CCNE1-amplified ovarian cancers. These findings uncover a heterochromatin-based mechanism of replication fork stabilization and suggest that CHAMP1 may represent a candidate therapeutic vulnerability in cancers with elevated RS.

The pathway affects the cellular sensitivity to oxidative stress and ferroptosis, revealing a previously uncharacterized layer of epigenetic control in lipid quality control and damage repair. This positions the LORD pathway as a promising therapeutic target for diseases linked to chronic inflammation, neurodegeneration and cancer.

The Cas9-degron retains activity and delivery efficiency comparable to conventional Cas9 in the absence of dTAG. Thus, this versatile system provides a superior alternative to conventional Cas9 and a powerful platform for in vivo CRISPR screening, gene function studies, and potentially temporally controlled gene therapy.

Moreover, NUSAP1 is identified as a novel HIF-repressed gene in TNBC cells, and its expression level shows a negative correlation with clinical outcomes in TNBC patients. These findings establish an HIF-NUSAP1 double-negative feedback loop in TNBC and validate TS-MAD as a potential therapeutic strategy for HIF-driven cancer.

Using a pre-clinical model, we further demonstrated that anti-SETDB1 therapy impairs tumor growth in vivo. Therefore, we not only provide evidence that SETDB1 plays a critical role in metastatic uveal melanoma cell growth, but we also identify SETDB1 as a novel relevant therapeutic target for the treatment of metastatic uveal melanoma.

Compared with sorafenib treatment alone, additional berberine treatment induced more severe mitochondrial dysfunction and ROS accumulation, following exacerbation of lipid peroxidation, which were abolished by ferroptosis inhibitors liproxstatin-1 and ferrostatin-1. Additionally, we demonstrated NQO1 activation induced by combined treatment was due to SETDB1 inactivation, following ERVs induction and genome instability, which may be another factor for lipid peroxidation and ferroptosis. Collectively, berberine has great potential to be used as a novel chemo-enhancer to improve the efficacy of sorafenib -based therapy.