Reference - Detail
| RRC ID | 78696 |
|---|---|
| Author | Ando K, Suenaga Y, Kamijo T. |
| Title | DNA Ligase 4 Contributes to Cell Proliferation against DNA-PK Inhibition in MYCN-Amplified Neuroblastoma IMR32 Cells. |
| Journal | Int J Mol Sci |
| Abstract |
Identifying the vulnerability of altered DNA repair machinery that displays synthetic lethality with MYCN amplification is a therapeutic rationale in unfavourable neuroblastoma. However, none of the inhibitors for DNA repair proteins are established as standard therapy in neuroblastoma. Here, we investigated whether DNA-PK inhibitor (DNA-PKi) could inhibit the proliferation of spheroids derived from neuroblastomas of MYCN transgenic mice and MYCN-amplified neuroblastoma cell lines. DNA-PKi exhibited an inhibitory effect on the proliferation of MYCN-driven neuroblastoma spheroids, whereas variable sensitivity was observed in those cell lines. Among them, the accelerated proliferation of IMR32 cells was dependent on DNA ligase 4 (LIG4), which comprises the canonical non-homologous end-joining pathway of DNA repair. Notably, LIG4 was identified as one of the worst prognostic factors in patients with MYCN-amplified neuroblastomas. It may play complementary roles in DNA-PK deficiency, suggesting the therapeutic potential of LIG4 inhibition in combination with DNA-PKi for MYCN-amplified neuroblastomas to overcome resistance to multimodal therapy. |
| Volume | 24(10) |
| Published | 2023-5-19 |
| DOI | 10.3390/ijms24109012 |
| PII | ijms24109012 |
| PMID | 37240360 |
| PMC | PMC10219512 |
| MeSH | Animals Cell Line, Tumor Cell Proliferation DNA Ligases / genetics DNA Ligases / metabolism DNA Repair* DNA-Activated Protein Kinase / genetics DNA-Activated Protein Kinase / metabolism Gene Amplification Gene Expression Regulation, Neoplastic Mice N-Myc Proto-Oncogene Protein / genetics N-Myc Proto-Oncogene Protein / metabolism Neuroblastoma* / drug therapy Neuroblastoma* / genetics Neuroblastoma* / metabolism |
| IF | 4.556 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | CHP-134(RCB0487) |