Effect of ceftriaxone treatment on gene expression of MYCN-amplified RB170
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE240841 | GEO | 2023/11/22
REPOSITORIES: GEO
Similar Datasets
Project description:Effect of ceftriaxone treatment on gene expression of MYCN-amplified RB170
| PRJNA1005399 | ENA
Project description:Retinoblastoma (RB) is a common malignancy that primarily affects pediatric populations. Although a well-known cause of RB is RB1 mutation, MYCN amplification can also lead to the disease, which is a poor prognosis factor. Studies conducted in various tumor types have shown that MYCN inhibition is an effective approach to impede tumor growth. Various indirect approaches have been developed to overcome the difficulty of directly targeting MYCN, such as modulating the super enhancer (SE) upstream of MYCN. The drug used in this study to treat MYCN-amplified RB was THZ1, a CDK7 inhibitor that can effectively suppress transcription by interfering with the activity of SEs. The study findings confirmed the anticancer activity of THZ1 against RB in both in vitro and in vivo experiments. Therapy with THZ1 was found to affect numerous genes in RB according to the RNA-seq analysis. Moreover, the gene expression changes induced by THZ1 treatment were enriched in ribosome, endocytosis, cell cycle, apoptosis, etc. Furthermore, the combined analysis of ChIP-Seq and RNA-seq data suggested a potential role of SEs in regulating the expression of critical transcription factors, such as MYCN, OTX2, and SOX4. Moreover, ChIP‒qPCR experiments were conducted to confirm the interaction between MYCN and SEs. In conclusion, THZ1 caused substantial changes in gene transcription in RB, resulting in inhibited cell proliferation, interference with the cell cycle, and increased apoptosis. The efficacy of THZ1 is positively correlated with the degree of MYCN amplification and is likely exerted by interfering with MYCN upstream SEs.
2023-07-04 | GSE236205 | GEO
Project description:Spinal Muscular Atrophy (SMA) is an autosomal recessive motor neuron disease and is the second most common genetic disorder leading to death in childhood. No effective therapy is currently available. It has been suggested that M-NM-2-lactam antibiotics such as ceftriaxone may offer neuroprotection in motoneuron disease. We investigated the therapeutic effect of ceftriaxone in a murine model of SMA. Microarray technology was used to assess the global gene expression profile of spinal cord obtained by ceftriaxone-treated and vehicle treated SMA mice. Comparative Gene Expression Analysis. The microarray data derived from three different groups: wildtype controls, transgenic SMA (vehicle treated) and ceftriaxone-treated SMA mice. Each population consists of four RNA profiling samples.
2013-12-01 | E-GEOD-19674 | biostudies-arrayexpress
Project description:MYCN amplification (MNA) is a defining feature of high-risk neuroblastoma (NB) that predicts poor prognosis. However, whether genes within or in close proximity to the MYCN amplicon also contribute to aggressiveness in MNA+ NB remains poorly understood. Here we identify that GREB1, a transcription factor encoding gene neighboring the MYCN locus, is frequently co-expressed with MYCN, and promotes cell survival in MNA+ NB. GREB1 controls gene expression independently of MYCN in MNA+ NB, among which we uncover Myosin 1B (MYO1B) as being highly expressed in MNA+ NB. MYO1B promotes aggressive features, including invasive capacity in vitro, as well as extravasation and distant metastasis in vivo. Global secretome and proteome profiling further delineate MYO1B as a major regulator of secretome reprogramming in MNA+ NB cells. Moreover, we identify the cytokine MIF as an important pro-invasive and pro-metastatic mediator of MYO1B activity. Together, we have identified a putative GREB1-MYO1B-MIF axis as an unconventional mechanism that promotes the aggressiveness of MNA+ NB, and independently of MYCN. Furthermore, we find that MYO1B is upregulated in association with other oncoproteins during cellular transformation, and is dramatically increased in multiple human cancer types, suggesting a crucial role of MYO1B in cancers in addition to MNA+ NB.
2023-10-24 | PXD039410 | Pride
Project description:Pisum sativum (cv. Kudrnac) seeds were obtained from SEMO a.s., Smržice, Czechia. All plants used for the study grew in the experimental field plot at Veletiny, Czechia (49°02'N 17°33'E; 195 m a.s.l.). Sowing was done after the rainfall on June 1, 2022, and plants were grown in a natural environment without any additional treatment. After 35 days, the field was divided into three blocks (mock, SAt1, SAt2), each containing approxi-mately 100 plants. For five weeks, plants were weekly sprayed with 1.5 L water solution supplemented with 0.025% (v/v) Silwet L-77 (mock; K), or 100 µM salicylic acid and Silwet (final concentration as for the mock; SA-a). The third set was treated as the mock for two weeks, followed by four weeks with salicylic acid treatment (SA-b).
2023-03-17 | PXD040506 | Pride
Project description:Neuroblastoma derived from primitive sympathetic neural precursors is a common type of solid tumor in infants. MYCN proto?oncogene bHLH transcription factor (MYCN) amplification and 1p36 deletion are important factors associated with the poor prognosis of neuroblastoma. Expression levels of MYCN and c?MYB proto?oncogene transcription factor (c?myb) decline during the differentiation of neuroblastoma cells; E2F transcription factor 1 (E2F1) activates the MYCN promoter. However, the underlying mechanism of MYCN overexpression and amplification requires further investigation. In the present study, potential c?Myb target genes, and the effect of c?myb RNA interference (RNAi) on MYCN expression and amplification were investigated in MYCN?amplified neuroblastoma cell lines. The mRNA expression levels and MYCN gene copy number in five neuroblastoma cell lines were determined by quantitative polymerase chain reaction. In addition, variations in potential target gene expression and MYCN gene copy number between pre? and post?c?myb RNAi treatment groups in MYCN?amplified Kelly, IMR32, SIMA and MHH?NB?11 cell lines, normalized to those of non?MYCN?amplified SH?SY5Y, were examined. To determine the associations between gene expression levels and chromosomal aberrations, MYCN amplification and 1p36 alterations in interphases/metaphases were analyzed using fluorescence in situ hybridization. Statistical analyses revealed correlations between 1p36 alterations and the expression of c?myb, MYB proto?oncogene like 2 (B?myb) and cyclin dependent kinase inhibitor 1A (p21). Additionally, the results of the present study also demonstrated that c?myb may be associated with E2F1 and L3MBTL1 histone methyl?lysine binding protein (L3MBTL1) expression, and that E2F1 may contribute to MYCN, B?myb, p21 and chromatin licensing and DNA replication factor 1 (hCdt1) expression, but to the repression of geminin (GMNN). On c?myb RNAi treatment, L3MBTL1 expression was silenced, while GMNN was upregulated, indicating G2/M arrest. In addition, MYCN gene copy number increased following treatment with c?myb RNAi. Notably, the present study also reported a 43.545% sequence identity between upstream of MYCN and Drosophila melanogaster amplification control element 3, suggesting that expression and/or amplification mechanisms of developmentally?regulated genes may be evolutionarily conserved. In conclusion, c?myb may be associated with regulating MYCN expression and amplification. c?myb, B?myb and p21 may also serve a role against chromosome 1p aberrations. Together, it was concluded that MYCN gene is amplified during S phase, potentially via a replication?based mechanism.
| S-EPMC6297758 | biostudies-literature
Project description:Study to examine changes in gene expression in C2C12 myotubes at 5 days post-differentiation following treatment with a non-damaging concentration of hydrogen peroxide) Keywords: parallel sample
2004-08-17 | GSE1678 | GEO
Project description:Spinal Muscular Atrophy (SMA) is an autosomal recessive motor neuron disease and is the second most common genetic disorder leading to death in childhood. No effective therapy is currently available. It has been suggested that β-lactam antibiotics such as ceftriaxone may offer neuroprotection in motoneuron disease. We investigated the therapeutic effect of ceftriaxone in a murine model of SMA. Microarray technology was used to assess the global gene expression profile of spinal cord obtained by ceftriaxone-treated and vehicle treated SMA mice.
2013-12-01 | GSE19674 | GEO
Project description:MYCN gene amplification and upregulated expression are major hallmarks in the progression of high-risk neuroblastoma. MYCN expression and function in modulating gene synthesis in neuroblastoma is controlled at virtually every level, including poorly understood regulation at the post-transcriptional level. MYCN modulates the expression of various microRNAs including the miR-17-92 cluster. MYCN mRNA expression itself is subjected to the control by miRNAs, most prominently the miR-17-92 cluster that balances MYCN expression by feed-back regulation. This homeostasis seems disturbed in neuroblastoma where MYCN upregulation coincides with severely increased expression of the miR-17-92 cluster. In the presented study, we applied high-throughput next generation sequencing to unravel the miRNome in a cohort of 97 neuroblastomas, representing all clinical stages. Aiming to reveal the MYCN-dependent miRNome, we evaluate miRNA expression in MYCN-amplified as well as none amplified tumor samples. In correlation with survival data analysis of differentially expressed miRNAs, we present various putative oncogenic as well as tumor suppressive miRNAs in neuroblastoma. Using microRNA trapping by RNA affinity purification, we provide a comprehensive view of MYCN-regulatory miRNAs in neuroblastoma-derived cells, confirming a pivotal role of the miR-17-92 cluster and moderate association by the let-7 miRNA family. Attempting to decipher how MYCN expression escapes elevated expression of inhibitory miRNAs, we present evidence that RNA-binding proteins like the IGF2 mRNA binding protein 1 reduce miRNA-directed downregulation of MYCN in neuroblastoma. Our findings emphasize the potency of post-transcriptional regulation of MYCN in neuroblastoma and unravel new avenues to pursue inhibition of this potent oncogene.
| S-EPMC8138323 | biostudies-literature
Project description:The MYC oncogenes and p53 have opposing yet interrelated roles in normal development and tumorigenesis. How MYCN expression alters the biology and clinical responsiveness of pediatric neuroblastoma remains poorly defined. Neuroblastoma is p53 wild type at diagnosis and repression of p53 signaling is required for tumorigenesis. Here, we tested the hypothesis that MYCN amplification alters p53 transcriptional activity in neuroblastoma. Interestingly, we found that MYCN directly binds to the tetrameric form of p53 at its C-terminal domain, and this interaction is independent of MYCN/MAX heterodimer formation. Chromatin analysis of MYCN and p53 targets reveals dramatic changes in binding, as well as co-localization of the MYCN-p53 complex at p53-REs and E-boxes of genes critical to DNA damage responses and cell cycle progression. RNA sequencing studies show that MYCN-p53 co-localization significantly modulated the expression of p53 target genes. Furthermore, MYCN-p53 interaction leads to regulation of alternative p53 targets not regulated in the presence of low MYCN levels. These novel targets include a number of genes involved in lipid metabolism, DNA repair, and apoptosis. Taken together, our findings demonstrate a novel oncogenic role of MYCN as a transcriptional co-regulator of p53 in high-risk MYCN amplified neuroblastoma. Targeting this novel oncogenic function of MYCN may enhance p53-mediated responses and sensitize MYCN amplified tumors to chemotherapy.
| S-EPMC5945521 | biostudies-literature