Inhibition of MYC by the SMARCB1 tumor suppressor

Weissmiller, April M.; Wang, Jing; Lorey, Shelly L.; Howard, Gregory C.; Martinez, Ernest; Liu, Qi; Tansey, William P.

doi:10.1038/s41467-019-10022-5

Cited by 65 publications

(108 citation statements)

References 54 publications

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“…SMACB1 was commonly downregulated in HF, KF, and KP. SMACB1 is a core subunit of the SWI/SNF (BAF) chromatin-remodeling complex and is well-recognized as a tumor suppressor gene, which is inactivated in aggressive cancers such as nearly all pediatric rhabdoid tumors [ 28 , 29 ]. These highly regulated common genes represent the typical gene signatures of various cells and nanoparticles.…”

Section: Resultsmentioning

confidence: 99%

Effects of Two Kinds of Iron Nanoparticles as Reactive Oxygen Species Inducer and Scavenger on the Transcriptomic Profiles of Two Human Leukemia Cells with Different Stemness

et al. 2020

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Leukemia is a common and lethal disease. In recent years, iron-based nanomedicines have been developed as a new ferroptosis inducer to leukemia. However, the cytotoxicity of iron nanoparticles to leukemia cells at the transcriptomic level remains unclear. This study investigated the effects of two kinds of iron nanoparticles, 2,3-Dimercaptosuccinic acid (DMSA)-coated Fe3O4 nanoparticles (FeNPs) as a reactive oxygen species (ROS) inducer and Prussian blue nanoparticles (PBNPs) as an ROS scavenger, on the transcriptomic profiles of two leukemia cells (KG1a and HL60) by RNA-Seq. As a result, 470 and 1690 differentially expressed genes (DEGs) were identified in the FeNP-treated HL60 and KG1a cells, respectively, and 2008 and 2504 DEGs were found in the PBNP-treated HL60 and KG1a cells, respectively. Among them, 14 common upregulated and 4 common downregulated DEGs were found, these genes were representative genes that play key roles in lipid metabolism (GBA and ABCA1), iron metabolism (FTL, DNM1, and TRFC), antioxidation (NQO1, GCLM, and SLC7A11), vesicle traffic (MCTP2, DNM1, STX3, and BIN2), and innate immune response (TLR6, ADGRG3, and DDX24). The gene ontology revealed that the mineral absorption pathway was significantly regulated by PBNPs in two cells, whereas the lipid metabolism and HIF-1 signaling pathways were significantly regulated by FeNPs in two cells. This study established the gene signatures of two kinds of nanoparticles in two leukemia cells, which revealed the main biological processes regulated by the two kinds of iron nanoparticles. These data shed new insights into the cytotoxicity of iron nanoparticles that differently regulate ROS in leukemia cells with variant stemness.

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Section: Resultsmentioning

confidence: 99%

Effects of Two Kinds of Iron Nanoparticles as Reactive Oxygen Species Inducer and Scavenger on the Transcriptomic Profiles of Two Human Leukemia Cells with Different Stemness

et al. 2020

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“…Carugo et al reported that the Myc-p53 axis regulates cellular proteostasis in SMARCB1-deficient malignant rhabdoid tumors [27]. Additionally, the SNF5 subunit encoded by SMARCB1 has been identified as an inhibitor that prevents the DNA-binding ability of Myc [26]. Together, these findings suggest that SMARCB1 deficiency is associated with an increased rate of protein synthesis and Myc activity in ATRTs, particularly in Myc-ATRTs, which may explain their high sensitivity to BTZ.…”

Section: Discussionmentioning

confidence: 98%

“…These results further support the link between Myc and protein synthesis in ATRT cells. Moreover, the correlation of Myc activity and SMARCB1-deficient cancers has been identified in priors studies [26][27][28]. Alimova et al found that SMARCB1-deficient ATRTs expressed higher Myc activity compare to normal brain tissues, regardless of the subtypes of ATRTs [28].…”

Section: Discussionmentioning

confidence: 98%

Upregulation of Protein Synthesis and Proteasome Degradation Confers Sensitivity to Proteasome Inhibitor Bortezomib in Myc-Atypical Teratoid/Rhabdoid Tumors

Tran

Sung

et al. 2020

Cancers

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Atypical teratoid rhabdoid tumors (ATRTs) are among the most malignant brain tumors in early childhood and remain incurable. Myc-ATRT is driven by the Myc oncogene, which directly controls the intracellular protein synthesis rate. Proteasome inhibitor bortezomib (BTZ) was approved by the Food and Drug Administration as a primary treatment for multiple myeloma. This study aimed to determine whether the upregulation of protein synthesis and proteasome degradation in Myc-ATRTs increases tumor cell sensitivity to BTZ. We performed differential gene expression and gene set enrichment analysis on matched primary and recurrent patient-derived xenograft (PDX) samples from an infant with ATRT. Concomitant upregulation of the Myc pathway, protein synthesis and proteasome degradation were identified in recurrent ATRTs. Additionally, we found the proteasome-encoding genes were highly expressed in ATRTs compared with in normal brain tissues, correlated with the malignancy of tumor cells and were essential for tumor cell survival. BTZ inhibited proliferation and induced apoptosis through the accumulation of p53 in three human Myc-ATRT cell lines (PDX-derived tumor cell line Re1-P6, BT-12 and CHLA-266). Furthermore, BTZ inhibited tumor growth and prolonged survival in Myc-ATRT orthotopic xenograft mice. Our findings suggest that BTZ may be a promising targeted therapy for Myc-ATRTs.

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“…This experimental finding is backed by studies in primary tumours, which found an overexpression of SHH components in a subgroup of ATRT [25]. Not only MYC‐dependent signalling but also the expression of MYC itself are also repressed by an intact SWI/SNF complex [54,55].…”

Section: Three Of a Kind? Structure And Functions Of Three Baf Complexesmentioning

confidence: 98%

Invited Review: Dysregulation of chromatin remodellers in paediatric brain tumours – SMARCB1 and beyond

Johann

2020

Neuropathology Appl Neurobio

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2020) Neuropathology and Applied Neurobiology 46, 57-72 Dysregulation of chromatin remodellers in paediatric brain tumours -SMARCB1 and beyond Mutations in chromatin remodelling genes occur in approximately 25% of all human tumours (Kadoch et al. Nat Genet 45: 592-601, 2013). The spectrum of alterations is broad and comprises single nucleotide variants, insertion/deletions and more complex structural variations. The single most often affected remodelling complex is the SWI/SNF complex (SWItch/sucrose non-fermentable). In the field of paediatric neuro-oncology, the spectrum of affected genes implicated in epigenetic remodelling is narrower with SMARCB1 and SMARCA4 being the most frequent.The low mutation frequencies in many of the SWI/SNF mutant entities underline the fact that perturbed chromatin remodelling is the most salient factor in tumourigenesis and could thus be a potential therapeutic opportunity. Here, I review the genetic basis of aberrant chromatin remodelling in paediatric brain tumours and discuss their impact on the epigenome in the respective entities, mainly medulloblastomas and rhabdoid tumours. Aberrations described in-Rhabdoid tumours eletions/SNVs (95% of all cases) -rare entities: INI1 deficient chordomas (10-20% of all cases), CRINET (all cases) Figure 1. An overview on SWItch/sucrose non-fermentable aberrant paediatric entities. CRINET, cribriform neuroepithelial tumours. Dysregulation of chromatin remodellers in paediatric neurooncology 61 CNS CRINET Point mutations CNS CRINET, cribriform neuroepithelial tumours.

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Inhibition of MYC by the SMARCB1 tumor suppressor

Cited by 65 publications

References 54 publications

Effects of Two Kinds of Iron Nanoparticles as Reactive Oxygen Species Inducer and Scavenger on the Transcriptomic Profiles of Two Human Leukemia Cells with Different Stemness

Effects of Two Kinds of Iron Nanoparticles as Reactive Oxygen Species Inducer and Scavenger on the Transcriptomic Profiles of Two Human Leukemia Cells with Different Stemness

Upregulation of Protein Synthesis and Proteasome Degradation Confers Sensitivity to Proteasome Inhibitor Bortezomib in Myc-Atypical Teratoid/Rhabdoid Tumors

Invited Review: Dysregulation of chromatin remodellers in paediatric brain tumours – SMARCB1 and beyond

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