Polycomb group protein BMI1 prevents neuroblastoma cells from DNA-damage-induced apoptotic cell death
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ABSTRACT:
PROVIDER: PRJNA783041 | ENA |
REPOSITORIES: ENA
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Project description:BMI1 is a polycomb protein and its overexpression has been correlated with cancer development and aggressiveness. We previously reported that v-myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog (MYCN)-induced BMI1 positively regulated neuroblastoma (NB) cell proliferation via the transcriptional suppression of tumor suppressors in NB cells. In order to evaluate the potential of BMI1 as a new target for NB therapy, we herein examined the effects of BMI1 reductions on NB cell differentiation and apoptotic NB cell death. BMI1 knockdown (KD) up to 7 days in NB cells significantly induced their differentiation. BMI1 depletion up to 14 days significantly induced apoptotic NB cell death along with the activation of p53, increases in p73, and induction of p53 family downstream molecules. BMI1 depletion in vivo markedly suppressed NB xenograft tumor growth. A pathological analysis using the TUNEL assay indicated the induction of apoptotic cell death. BMI1 reductions activated ATM and increased γ-H2AX in NB cells. Importantly, these DNA damage signals and apoptotic cell death were not canceled by transduction of polycomb group molecules EZH2 and RING1B. Further, EZH2 or RING1B knockdown could not induce apoptotic NB cell death at the same level of BMI1 KD. Together, BMI1 appears to be a promising target of molecular therapy for NB tumors and our report clarified, for the first time, the shared role of PcG proteins in DNA damage response of NB cells.
2022-11-08 | GSE189449 | GEO
Project description:Mus musculus Bmi1, Bmi1 polycomb ring finger oncogene [Source:MGI Symbol;Acc:MGI:88174], is differentially expressed in 101 experiment(s);
| ENSMUSG00000026739 | ExpressionAtlas
Project description:Rattus norvegicus Bmi1, BMI1 proto-oncogene, polycomb ring finger [Source:RGD Symbol;Acc:1307403], is differentially expressed in 2 experiment(s);
| ENSRNOG00000016585 | ExpressionAtlas
Project description:Rattus norvegicus Bmi1, BMI1 proto-oncogene, polycomb ring finger [Source:RGD Symbol;Acc:1307403], is expressed in 5 baseline experiment(s);
| ENSRNOG00000016585 | ExpressionAtlas
Project description:Mus musculus Bmi1, Bmi1 polycomb ring finger oncogene [Source:MGI Symbol;Acc:MGI:88174], is expressed in 36 baseline experiment(s);
| ENSMUSG00000026739 | ExpressionAtlas
Project description:Bmi1 is a component of the Polycomb-repressive complexes (PRC) and essential for maintaining the pool of adult stem cells. PRC are key regulators for embryonic development by modifying chromatin architecture and maintaining gene repression. To assess the role of Bmi1 in pluripotent stem cells and upon exit from pluripotency during differentiation, we studied forced Bmi1 expression in mouse embryonic stem cells (ESC). We found that ESC do not express detectable levels of Bmi1 RNA and protein and that forced Bmi1 expression had no obvious influence on ESC self-renewal. However, upon ESC differentiation Bmi1 effectively enhanced development of hematopoietic cells. Global transcriptional profiling identified a large array of genes that were differentially regulated during ESC differentiation by Bmi1. Importantly, we found that Bmi1 induced a prominent up-regulation of Gata2, a zinc finger transcription factor, which is essential for primitive hematopoietic cell generation from mesoderm. In addition, Bmi1 caused sustained growth and a more than 100-fold expansion of ESC-derived hematopoietic stem/progenitor cells within 2-3 weeks of culture. The enhanced proliferative capacity was associated with reduced Ink4a/Arf expression in Bmi1-transduced cells. Taken together, our experiments demonstrate distinct activities of Bmi1 in ESC and ESC-derived hematopoietic progenitor cells. In addition, Bmi1 enhances the propensity of ESC in differentiating towards the hematopoietic lineage. Thus, Bmi1 could be a candidate gene for engineered adult stem cell derivation from ESC.
2011-04-29 | GSE20958 | GEO
Project description:Bmi1 is a component of the Polycomb-repressive complexes (PRC) and essential for maintaining the pool of adult stem cells. PRC are key regulators for embryonic development by modifying chromatin architecture and maintaining gene repression. To assess the role of Bmi1 in pluripotent stem cells and upon exit from pluripotency during differentiation, we studied forced Bmi1 expression in mouse embryonic stem cells (ESC). We found that ESC do not express detectable levels of Bmi1 RNA and protein and that forced Bmi1 expression had no obvious influence on ESC self-renewal. However, upon ESC differentiation Bmi1 effectively enhanced development of hematopoietic cells. Global transcriptional profiling identified a large array of genes that were differentially regulated during ESC differentiation by Bmi1. Importantly, we found that Bmi1 induced a prominent up-regulation of Gata2, a zinc finger transcription factor, which is essential for primitive hematopoietic cell generation from mesoderm. In addition, Bmi1 caused sustained growth and a more than 100-fold expansion of ESC-derived hematopoietic stem/progenitor cells within 2-3 weeks of culture. The enhanced proliferative capacity was associated with reduced Ink4a/Arf expression in Bmi1-transduced cells. Taken together, our experiments demonstrate distinct activities of Bmi1 in ESC and ESC-derived hematopoietic progenitor cells. In addition, Bmi1 enhances the propensity of ESC in differentiating towards the hematopoietic lineage. Thus, Bmi1 could be a candidate gene for engineered adult stem cell derivation from ESC. 8 samples in total. Bmi1 embryonic stem cells sample_1 (Bmi1_ESC_1) Bmi1 embryonic stem cells sample_2 (Bmi1_ESC_2) Untreated CCE embryonic stem cells (CCE_ESC_Control) Empty vector CCE embryonic stem cells (CCE_ESC_Vector) Bmi1 embryoid body sample_1 (Bmi1_EB_1) Bmi1 embryoid body sample_2 (Bmi1_EB_2) Empty vector control embryoid body sample_1 (Vector_EB_1) Empty vector control embryoid body sample_2 (Vector_EB_2)
2011-04-29 | E-GEOD-20958 | biostudies-arrayexpress
Project description:Oryctolagus cuniculus BMI1, BMI1 proto-oncogene, polycomb ring finger [Source:HGNC Symbol;Acc:HGNC:1066], is expressed in 1 baseline experiment(s);
| ENSOCUG00000005420 | ExpressionAtlas
Project description:Homo sapiens BMI1, BMI1 proto-oncogene, polycomb ring finger [Source:HGNC Symbol;Acc:HGNC:1066], is expressed in 43 baseline experiment(s);
| ENSG00000168283 | ExpressionAtlas
Project description:Homo sapiens BMI1, BMI1 proto-oncogene, polycomb ring finger [Source:HGNC Symbol;Acc:HGNC:1066], is differentially expressed in 152 experiment(s);
| ENSG00000168283 | ExpressionAtlas