MYCN expression

MYCN acts on termination through its direct binding to the 3' region of genes and it interacts with DDX17, suggesting that it may interfere with the activity of the helicase. Collectively, our work reveals a novel function of MYCN in transcription termination and suggests that the deregulation of MYCN and DDX17/DDX5 expression in neuroblastoma may lead to the expression of non-canonical and potentially harmful RNA molecules.

The NB‑MSI2 + MYCN+ subtype defines a clinically aggressive, therapy‑refractory state characterized by high proliferation, metabolic reprogramming, and immunosuppression. For patients with MYCN-amplified NB, MSI2 is both a prognostic biomarker and a candidate therapeutic target.

In SK-BE (2) cells, these ASO prodrugs, particularly the R3‑5 and R5‑5 sequences, effectively silenced MYCN expression and induced apoptosis. This work provides a rational structure‑activity design strategy for tumor‑microenvironment‑responsive nucleic acid therapeutics and establishes a reference for further structural optimization.

Everolimus (EVER) and tozasertib (TOZA) encapsulated in NP and targeted with dinutuximab β (DTX-β). DTX-β/EVER-TOZA@PEG-b-PLGA may exert cytotoxic and apoptotic effects in NB. The use of targeted nanocarriers in NB treatment may enhance cytotoxic and apoptotic responses specifically in the tumor region.

High-level expression of Oct-1Z increased expression of MYCN and its target gene NEUROD1. Oct-1Z was thus identified as an activator of MYCN expression and a potential target for neuroblastoma therapy in patients with high levels of MYCN.

Additionally, MYCN-induced miR-221 was found to suppress CREB expression. Together, these findings demonstrate MYCN-dependent effects of TrkC signalling and highlight the therapeutic potential of targeting the PKA pathway to induce differentiation in high-risk MYCN-amplified neuroblastoma.

It eliminates both non-MYCN-amplified (SH-SY5Y and SK-N-SH) and MYCN-amplified (SMS-KCNR) NB cells that exhibit PMA-inducible CCL2 expression but not MYCN-amplified NB cells (IMR-32 and NB-1) that exhibit CCL2 repression, and is offset by reciprocal NB cell-induced Fas-mediated Jurkat cell apoptosis. These findings form a solid foundation for further pre-clinical development aimed at identifying clinically relevant physiological immune cell equivalents and alternative PKC activators, with the ultimate goal of translating this mechanism into an effective immune-therapeutic approach for the treatment of high-risk non-immunogenic NBs, especially NBs that exhibit CCL2 and TrkAIII expression.

Leveraging this property, neuroblastoma-derived exosomes can be purified, modified, and loaded with small interfering RNA (siRNA) to silence MYCN expression, combined with chloroquine-an FDA-approved autophagy inhibitor-to simultaneously inhibit autophagy and induce apoptotic signaling...Collectively, exosome-based strategies represent a paradigm shift in formulating combination therapies, offering a multifaceted approach to target MYCN amplification, inhibit autophagy, induce apoptosis, and modulate the tumor-microbiome axis. These innovations hold significant promise for improving clinical outcomes in high-risk MYCN-amplified neuroblastoma patients.

Conversely, in prostate adenocarcinoma models, DNMT1 deletion leads to de-repression of neuroendocrine lineage genes with a loss of H3K27me3 marks. Our findings reveal a functional interplay between two repressive epigenetic machineries that mediates lineage plasticity in prostate cancer.

This score reliably predicted recurrence risk and identified EMT-prone microenvironments, with stronger predictive performance in nontumor tissues, suggesting its potential in detecting precancerous niches predisposed to de novo tumorigenesis. Collectively, our findings establish MYCN as a functional driver and spatial marker of tumor-promoting microenvironments in liver tumorigenesis; additionally, we propose a clinically actionable strategy to identify high-risk patients through transcriptomic profiling of nontumor liver tissue.

P1, N=26, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed

Notably, MI102 effect exhibited superior tumor cell selectivity compared with the MET inhibitor tivantinib. At the transcriptional level, RNA-seq revealed that MI102 globally downregulated MYCN-associated oncogenic programs. Collectively, these findings establish pharmacological downregulation of MYCN as a promising therapeutic strategy for HCC and reveal a functional link between MET signaling and MYCN-driven oncogenic pathways.