Reference - Detail
| RRC ID | 83511 |
|---|---|
| Author | Okada R, Takenobu H, Satoh S, Sugino RP, Onuki R, Haruta M, Mukae K, Nakazawa A, Akter J, Ohira M, Kamijo T. |
| Title | L3MBTL2 maintains MYCN-amplified neuroblastoma cell proliferation through silencing NRIP3 and BRME1 genes. |
| Journal | Genes Cells |
| Abstract |
Epigenetic alterations critically affect tumor development. Polycomb-group complexes constitute an evolutionarily conserved epigenetic machinery that regulates stem cell fate and development. They are implicated in tumorigenesis, primarily via histone modification. Polycomb repressive complex 1 (PRC1) complexes 1-6 (PRC1.1-6) mediate the ubiquitination of histone H2A on lysine 119 (H2AK119ub). Here, we studied the functional roles of a PRC1.6 molecule, L3MBTL2, in neuroblastoma (NB) cells. L3MBTL2-knockout and knockdown revealed that L3MBTL2 depletion suppressed NB cell proliferation via cell-cycle arrest and gamma-H2A.X upregulation. L3MBTL2-knockout profoundly suppressed xenograft tumor formation. Transcriptome analysis revealed suppressed cell-cycle-related and activated differentiation-related pathways. Break repair meiotic recombinase recruitment factor 1 (BRME1) and nuclear receptor interacting protein 3 (NRIP3) were notably de-repressed by L3MBTL2-knockout. The deletion of L3MBTL2 reduced enrichment of H2AK119ub and PCGF6 at transcriptional start site proximal regions of the targets. Add-back studies unveiled the importance of L3MBTL2-BRME1 and -NRIP3 axes for NB cell proliferation. We further manifested the association of MYCN with de-repression of NRIP3 in an L3MBTL2-deficient context. Therefore, this study first revealed the significance of L3MBTL2-mediated gene silencing in MYCN-amplified NB cells. |
| Volume | 29(10) |
| Pages | 838-853 |
| Published | 2024-10-1 |
| DOI | 10.1111/gtc.13148 |
| PMID | 39189159 |
| MeSH | Animals Cell Line, Tumor Cell Proliferation* Gene Expression Regulation, Neoplastic Gene Silencing Histones / metabolism Humans Membrane Proteins / genetics Membrane Proteins / metabolism Mice Mice, Nude N-Myc Proto-Oncogene Protein* / genetics N-Myc Proto-Oncogene Protein* / metabolism Neuroblastoma* / genetics Neuroblastoma* / metabolism Neuroblastoma* / pathology |
| IF | 1.655 |
| 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 | NB-1(RCB1953) |