AEBP1 (AE Binding Protein 1)

Fibroblasts drive glioma recurrence, with AEBP1, ZNF708, and TSHZ2 predicting recurrence and chemoresistance. These genes promote immune suppression (via plasma cells) and activate recurrence pathways. Oligodendrocyte-astrocyte interactions shape the recurrent microenvironment, suggesting new therapeutic targets.

In summary, our research established the ARG-derived prognostic signature validated across independent GBM cohorts and revealed concomitant immune and mechanical niche dysregulation in high-risk patients. The rationale for combined angiogenesis/stroma/immune modulation strategies was provided, with FSCN1 proposed as the potential therapeutic target.

Functional experiments using three-dimensional (3D) spheroids composed of oral squamous cell carcinoma (OSCC)-derived CAFs showed that AEBP1 knockdown significantly reduced spheroid stiffness without altering their morphology or size, indicating that ACLP contributes to the mechanical properties of tumor tissues. Together with earlier findings linking AEBP1/ACLP to reduced CD8+ T-cell infiltration, our results suggest that stromal AEBP1/ACLP enhances both extracellular matrix stiffness and immune suppression and highlights AEBP1/ACLP as a potential therapeutic target through which to remodel the tumor microenvironment and improve anti-tumor immunity.

Immunofluorescent double staining was used to examine the co-expression of CD31 in α-SMA-positive CAFs to identify whether the endothelial-to-mesenchymal transition (EndoMT) is involved in the origin, and obvious colocalization was observed. Visium and Visium HD spatial transcriptomics further revealed endothelial cells (ECs) exhibited remarkable co-expression of CAF-specific marker genes and revealed inferred developmental trajectories to CAFs; molecular determinants, including TIMP1, IGFBP7, THBS2, CD74, COL4A1, COL4A2, AEBP1, S100A6, KCTD12, CALD1, IGHG1, SERPINE1, MCL1, MGP, GSTP1, TAGLN, THBS1, and CTGF, were positively correlated with the spatial developmental trajectories of ECs to CAFs; and CTGF exhibited extensive interactions with other common positively correlated molecular determinants and was a highly connected node in the interaction network. ECs that undergo EndoMT may be one of the potential cellular and mechanical origins of CAFs in HCC, and the development of EndoMT may be associated with CTGF.

This study reveals immune-molecular interactions in GBM, identifies AEBP1/EFEMP2 as prognostic markers, and proposes targeted therapies for personalized treatment.

Our findings indicate that AEBP1 plays a crucial role in regulating the function of CAFs within the TME. Targeting AEBP1 could be a promising strategy to inhibit the tumor-promoting activities of CAFs and to overcome resistance to anti-PD-1 immunotherapy.

Both genetic and pharmacological AEBP1 inhibition synergize with immune checkpoint blockade in syngeneic models. Our study establishes AEBP1 as a key regulator of CAF-mediated T cell dysfunction and a therapeutic target.

It identifies potential molecular mechanisms and therapeutic candidates. Further clinical trials are needed to validate the efficacy of resveratrol and explore its structure-activity relationships to develop targeted treatments.

Gradual DNAm changes were found to align with progression of MASLD and EAA, with EAA a potential nonbiased quantitative biomarker for MASLD. Integrative analysis highlighted potential new therapeutic transcription factor targets, with special emphasis on AEBP1 and emerging nuclear receptors including CAR(NR1I3), MR(NR3C2), GR(NR3C1), and ESRRG, underscoring the potential of epigenetic redox-metabolic therapies for MASLD.

AEBP1 knockdown reduced the protein levels of GLI1, and treatment with the GLI-specific inhibitor GANT61 induced markers that were not suppressed by the forced expression of AEBP1. These findings suggest that AEBP1-mediated GLI1 expression reduces the FACT complex dependency of bladder cancer cell survival.

Our results suggest that HGSC can be classified based on lncRNA expression and characterized using molecular features. Therefore, lncRNAs and MTFs may synergistically contribute to molecular features of HGSC that could be indicators for personalized medicine.

Notably, the silencing of AEBP1 counteracted the activation of the AKT signaling pathway induced by an activator. In conclusion, the findings of the present study indicated that silencing of AEBP1 suppressed OS proliferation, revealing AEBP1 as a promising therapeutic target for OS treatment.