| 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
|
| Resource |
| Human and Animal Cells |
NB-1(RCB1953) |
