Table 1.
Most of the 11 c-Myc-interacting, HR signature genes have been studied as anti-NB drug targets, further highlighting the critical role of c-Myc in HR-NB.
| Gene Symbol | MYCN-dep. | Drug | Pubmed | Experimental cells | Response to drug(s) | Potential mechanism |
|---|---|---|---|---|---|---|
| CAD | MA > MN | N-L-aspartate (PALA) | 9418900 | REF52 cells | amplification | increase expression of n-Myc and overcome the PALA-induced cell cycle block |
| CCNB1 | MA > MN | Lupiwighteone; Thymoquinone | 25661352; 26745078 | SY5Y; Neuro-2a | decrease/decrease | induce G2/M phase arrest |
| EIF4E | MA > MN | MNK inhibition | 25743081 | lung etc | inhibition | MNK inhibitors inhibit eIF4E phosphorylation, colony formation, epithelial-to-mesenchymal transition, invasion and MCL1 expression in cancer |
| EIF4G1 | MA > MN | NBT-272 | 20889731 | SH-SY5Y xenograft model | interacting partner EIF4E is inhibited | arrest tumour growth through AKT and the MEK/extracellular signal-regulated kinase pathways |
| PCNA | MA > MN | Thymoquinone | 26745078 | Neuro-2a | decrease | arrest the cell-cycle in the G2/M phase and induce apoptosis |
| RUVBL2 | MA > MN | PCI-24781 | 23977108 | SK-N-DZ | knockdown of RuvBL2 rescued cells from PCI-24781-induced cell death | histone deacetylase inhibitor |
| CCND1 | MN > MA | Lupiwighteone | 25661352 | SY5Y | decrease | induce G2/M phase arrest |
| CDKN1A | MN > MA | Doxorubicin | 26284262 | IMR-32 | decrease | blocking an enzyme called topo isomerase 2 that cancer cells need to divide and grow |
| MYC | MN > MA | PD166285 and 3-DAZA | 25477524 | SK-N-AS, SH-SY5Y, IMR-32, SK-NBE (2), LAN1, NB19 | decrease the expression of AHCY, BLM, PKMYT1, and CKS1B | growth arrest in the G1 phase of the cell cycle of MYCN-negative |
| NRAS | MN > MA | trametinib, GSK2126458, GSK690693 | 25277205 | SK-N-AS, CHP212 and SK-N-DZ | Decrease the NRAS expression | MEK and PI3K/mTOR inhibitor synergistically decreases cell viability in NRAS Q61 mutant NB cell lines |