BHLHE40 (Basic Helix-Loop-Helix Family Member E40)

These findings establish lncRNAs as key regulators of tumor immunity and uncover a critical link between genetic risk, lncRNAs, cancer immunosurveillance and breast cancer development, positioning BRRIAR as a promising lncRNA-based RIG-I activator for ER + breast cancer therapy.

In TLSs, TGF-β orchestrated BHLHE40 expression in TRM and effector TRM differentiation. Our findings identified an effector subset of TRM as CD49a+PD1hi CD8+ TRM, and highlighted a BHLHE40-orchestrated, resident immune component, rather than circulating cells, as a major contributor to allograft rejection.

Collectively, our findings demonstrate that BHLHE40 promotes EMT and metastasis in cervical cancer by transcriptionally activating ANGPTL3, whereas digoxin exerts anti-EMT effects by targeting this axis. These data highlight the critical role of the BHLHE40-ANGPTL3 axis in cervical cancer progression and suggest that repurposing digoxin offers a novel therapeutic strategy for suppressing EMT in this disease.

Single-cell transcriptomics revealed that tumor-infiltrating CD8+T cells in patients responding to PD-1 antibody treatment had higher hnRNPA2B1 expression compared with nonresponders. In summary, our study indicates that tumor-infiltrating CD103+CD8+hnRNPA2B1+ tissue-resident T cells can serve as predictive factors and indicators for unfavorable prognosis and patient responses to PD-1 treatment outcomes in ccRCC patients.

BHLHE40 curbed ferroptosis and oxidative stress of GC cells by modulating the expression of RGS16, thereby facilitating the malignant progression of GC.

BHLHE40 is significantly correlated with PDAC malignancy and chemoresistance via SAT1 regulation and immune evasion. Targeting BHLHE40 may sensitize PDACs to Gemcitabine and facilitate personalized treatment for BHLHE40+ PDAC patients.

This study identifies key T cell and macrophage subsets mediating the efficacy of immunotherapy in overcoming immune escape in both MMRd and MMRp CRC settings. Anti-PD-1 therapy leads to the accumulation and colocalization of MHCI/II+ C1Q+ CXCL9+ macrophages and DCs with TCF+ CCL5+ T cells that have high TCR diversity.Resistance to anti-PD-1 therapy involves multiple T cell checkpoints, TREM2+ macrophages, IL1B+ TREM1+ monocytes and neutrophils, and IFITM+ tumor cells.Simultaneous blockade of PD-1, LAG3, CTLA-4 and TREM2 dramatically prevents progression of both MMRd and MMRp tumors.Combination therapy completely eliminates tumors by leveraging MHC+ macrophage, CD4+ and CD8+ T cell interactions, facilitating durable anti-tumor effects.

Conclusion BHLHE40 is highly expressed in OS tissues, and its knockdown can significantly inhibit OS cell proliferation, migration, and invasion, while reducing PI3K/AKT signaling pathway activity. This suggests that BHLHE40 could serve as a novel therapeutic target for OS.

Three novel feed-back loops and a novel AR- BHLHE40 / LYL1 -p27kip1 axis has been identified mediating cellular senescence in PCa cells.

Overexpression of GRIN2D promoted calcium efflux, phosphorylation of p38 MARK protein, and proliferation of GES1 cells. Altogether, the findings derived from this study suggest that BHLHE40 knockdown suppresses the growth, mobility, and glycolysis of GC cells by inhibiting GRIN2D transcription and disrupting the BHLHE40/GRIN2D axis may be an attractive therapeutic strategy for GC.

TREM2 blockade enhances neoAg vaccine efficacy and is associated with fewer CX3CR1+CD206+ macrophages and induction of neoAg-specific CD8 T cells. Our findings highlight different mechanisms underlying neoAg vaccines and different forms of ICT and identify combinatorial therapies to enhance neoAg vaccine efficacy.

BHLHE40 mediates the transcriptional activation of NEAT1, which activates the Wnt/β-catenin pathway and promotes the CRC progression.