TRIM28 (Tripartite Motif Containing 28)

pneumoniae suppressed S-nitrosylation of tripartite motif containing protein 28 (TRIM28) by diminishing Mn2+ levels, allowing TRIM28 to physically interact with the transcription factor SP1 to promote the transcription of solute carrier family 27 member 1 (SLC27A1) and lipid deposition. Taken together, these findings indicate that tumor-resident S. pneumoniae plays an important role in conferring pazopanib resistance, suggesting that S. pneumoniae could serve as a potential biomarker of pazopanib response in ccRCC.

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.

In OC mice, TRIM28 overexpression promotes angiogenesis and Bev resistance via ESM1-mediated ITGB1/FAK activation. This work unveils a new molecular pathway underlying Bev resistance in OC and proposes TRIM28 and ESM1 as potential therapeutic targets.

Functionally, SULF1 depletion impaired melanoma cell migration and invasion in vitro and reduced spontaneous metastasis in an orthotopic xenograft model. Together, these findings define an epigenetic axis linking chromatin regulation to extracellular glycan remodeling and identify HS-modifying enzymes as candidate targets to limit melanoma metastasis.

In functional measurements, HDAC suppression primarily increased excitability, while SIRT suppression decreased excitability, in line with transcriptomic links. Our analysis offers insights about the role of epigenetic modifiers in regulating cardiac electrophysiology and informs the utility of hiPSC-CM as a scalable experimental model for cardiotoxicity testing of HDAC inhibitors.

Our findings elucidate a key mechanism by which F. nucleatum survives and promotes treatment resistance in NPC, providing a microbiological prognosis indicator for NPC patients.

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.

This study reveals a novel molecular mechanism through which ginsenoside Rg3 antagonises endometriosis, providing a critical theoretical basis and experimental foundation for the development of new targeted therapeutic strategies against this disease.

However, Trim28 deletion also led to excessive deposition of tumor extracellular matrix (ECM). Our findings suggest that ECM alterations downstream of ERV derepression could affect immune cells in the tumor microenvironment and may promote tumor progression.

Four lead compounds were identified, with compound C87 exhibiting the most favorable binding free energy (ΔGbind = -57.2 kcal/mol) and stable interactions throughout molecular dynamics simulations. These findings highlight the potential of covalent inhibition as a novel strategy to disrupt oncogenic TRIM28-EZH2 complexes and restore tumor suppressor gene expression.

Lastly, by preventing degradation of SRSF3, we were able to reduce tumors in a diethyl-nitrosamine-induced (DEN-induced) model of cirrhotic HCC. These findings suggest that maintenance of SRSF3 protein stability is crucial for preventing DNA damage and protecting liver from early metabolic liver disease and progression to HCC.

In addition, recombinant PDZRN4 or screened small molecules retinoic acid showed potent inhibitory effects on EGFR-driven LUAD growth and amelioration of osimertinib resistance...Graphical Abstract: Germline variation rs74955204 (p.G121E, c.362 G > A) in PDZRN4 significantly upregulated PDZRN4 expression and resulted in indolent growth of LUAD. Overexpressed PDZRN4 inhibits the ubiquitylation of HIF-1A by TRIM28, activating HIF-1A-IGFBP3 signaling to promote apoptosis, and inducing NDRG1 to inhibit EGFR-AKT signaling, thus restricting lung cancer cell growth.