MYCN expression

Molecular docking and molecular dynamic simulation revealed that CCA-1.1 interacted with both N-Myc and c-Myc. Our findings demonstrate CCA-1.1 as a distinctive anti-cancer candidate for HCC driven by MYC activation.

We thus provide, for the first time, evidence that HMMR does have oncoprotein-like properties in neuroblastoma cells and that HMMR expression has potential as a prognostic marker. Moreover, initial biochemical analyses highlight a potential influence for HMMR in MTOR and DDR pathway regulation.

In summary, the present study demonstrated that RP11-196G11.6 may inhibit NB progression by sponging miR-376a-3p, leading to the upregulation of RYBP expression and consequently inhibiting NB progression. These findings revealed a novel lncRNA-miRNA axis involved in NB pathogenesis.

P1, N=26, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Oct 2025 --> Feb 2026 | Trial primary completion date: Oct 2025 --> Jan 2026

The DPI and MitoQ combination further synergizes with vincristine, a chemotherapeutic agent used in NB treatment. Phosphoproteomics and proteomics analysis suggests that the drug combination induces MNA NB cell death by arresting the cell cycle and inhibiting oxidative phosphorylation (OXPHOS) in the mitochondria. Thus, interference with mitochondrial metabolism may represent an effective strategy to enhance the activity of chemotherapeutic drugs in MNA-NB.

The antiproliferative effects of JQ1 and vincristine were comparable, and there was trend towards reduced and delayed xenograft growth in JQ1-treated mice. We conclude that confirmatory preclinical trials allow for robust assessment of the efficacy of candidate interventions and reduce bias in academic research. The study platform established here provides a framework that may be of particular benefit for the development of new drugs for rare cancers.

Thus, the half-maximal inhibitory concentration was measured and cisplatin treatment assay was carried out...Finally, we demonstrated that DLX5 which was transcriptionally activated by MYCN, promoted growth, metastasis and chemoresistance of neuroblastoma through enhanced AKT phosphorylation. The findings in our study provided new insight for progression and chemoresistance of neuroblastoma.

Our findings show that high levels of HIF2α in neuroblastoma, leads to drastically reduced MYCN protein levels, cell cycle exit, and noradrenergic cell differentiation. Taken together, our results challenge the dogma that HIF2α acts as an oncogene in neuroblastoma.

Moreover, our model predicts a potential bistability of cellular metabolism with a low-flux state likely representing a non-proliferative state. Overall, our study emphasizes that perturbations such as expression changes should be analysed in the context of realistic pathway models, in which specific interactions and complex regulations are captured.

Pharmacological screening further identified distinct therapeutic vulnerabilities, demonstrating distinct subtype-specific sensitivity of MYCN-driven cells to transcriptional inhibitors (THZ1, Flavopiridol) and the cell-cycle inhibitor Volasertib, indicative of a unique oncogene-addicted state compared to RB1-deficient retinoblastoma cells. Collectively, our study elucidates the developmental and molecular mechanisms underpinning MYCN-driven retinoblastoma, establishes a robust and clinically relevant human retinal organoid platform, and highlights targeted transcriptional inhibition as a promising therapeutic approach for this aggressive pediatric cancer subtype.

While chemotherapies such as sorafenib is effective for some patients, others show poor responses, necessitating new treatments...In a xenograft model, PGV-1 significantly reduced tumor formation and growth. These findings highlight PGV-1's potential as a targeted therapy for MYCN-overexpressing HCC, warranting further development.

These transcriptional changes are accompanied by decreased neuroblastoma cell proliferation and increased neuronal differentiation, reflecting impaired regulation of MYCN target genes upon NIPBL loss. Collectively, we have established a mechanistic link between NIPBL and the MYCN-driven transcriptome, highlighting NIPBL as a potential therapeutic vulnerability to promote differentiation in high-risk neuroblastoma.