GEO accession GSE255957 is currently private and is scheduled to be released on Dec 31, 2025.
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ABSTRACT:
PROVIDER: PRJNA1077298 | ENA |
REPOSITORIES: ENA
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Project description:Therapeutic options for metastatic or recurrent osteosarcoma are limited. Gemcitabine and 12 docetaxel combination is used as second-line therapy for this disease. Bromodomain-containing 13 protein 4 (BRD4) plays essential roles in regulating autophagy in several human diseases and is 14 overexpressed in osteosarcoma. Thus, in the current study, we investigated whether BRD4 is 15 involved in the modulation of gemcitabine-induced autophagy in osteosarcoma. We confirmed 16 that gemcitabine induced autophagic flux in LM7 and CCH-OS-D human osteosarcoma cell lines. 17 Furthermore, we found that gemcitabine induced BRD4 protein and mRNA expression in a time-18 dependent manner in LM7 cells and also in CCH-OS-D cells but only at the mRNA level. Moreover, 19 gemcitabine induced CCAAT/enhancer binding protein beta (C/EBPβ), a transcription factor 20 known to regulate autophagy. We further showed that C/EBPβ induction was mediated by BRD4 21 as inhibition of BRD4 blocked its induction. Furthermore, we demonstrated that gemcitabine-22 induced C/EBPβ bound to BRD4. Because inhibition of BRD4 diminished autophagic flux, we 23 conclude that BRD4 may act as an epigenetic regulator of gemcitabine-induced autophagy in 24 osteosarcoma via C/EBPβ. Additionally, because inhibition of BRD4 in gemcitabine treated 25 osteosarcoma cells led to different outcomes, our data suggests the potential for the BRD4- 26 C/EBPβ interaction to define gemcitabine-induced autophagy outcome in osteosarcoma.
2025-12-31 | GSE255957 | GEO
Project description:Therapeutic options for metastatic or recurrent osteosarcoma are limited. Gemcitabine and 12 docetaxel combination is used as second-line therapy for this disease. Bromodomain-containing 13 protein 4 (BRD4) plays essential roles in regulating autophagy in several human diseases and is 14 overexpressed in osteosarcoma. Thus, in the current study, we investigated whether BRD4 is 15 involved in the modulation of gemcitabine-induced autophagy in osteosarcoma. We confirmed 16 that gemcitabine induced autophagic flux in LM7 and CCH-OS-D human osteosarcoma cell lines. 17 Furthermore, we found that gemcitabine induced BRD4 protein and mRNA expression in a time-18 dependent manner in LM7 cells and also in CCH-OS-D cells but only at the mRNA level. Moreover, 19 gemcitabine induced CCAAT/enhancer binding protein beta (C/EBPβ), a transcription factor 20 known to regulate autophagy. We further showed that C/EBPβ induction was mediated by BRD4 21 as inhibition of BRD4 blocked its induction. Furthermore, we demonstrated that gemcitabine-22 induced C/EBPβ bound to BRD4. Because inhibition of BRD4 diminished autophagic flux, we 23 conclude that BRD4 may act as an epigenetic regulator of gemcitabine-induced autophagy in 24 osteosarcoma via C/EBPβ. Additionally, because inhibition of BRD4 in gemcitabine treated 25 osteosarcoma cells led to different outcomes, our data suggests the potential for the BRD4- 26 C/EBPβ interaction to define gemcitabine-induced autophagy outcome in osteosarcoma.
2025-12-31 | GSE255956 | GEO
Project description:BRD4 Regulates Gemcitabine Efficacy by Modulating Autophagy Activity in Osteosarcoma Cells [Cell lines]
| PRJNA1077299 | ENA
Project description:Autophagy is a membrane-trafficking process that directs degradation of cytoplasmic material in lysosomes. The process promotes cellular fidelity, and while the core machinery of autophagy is known, the mechanisms that promote and sustain autophagy are less well defined. Here we report that the epigenetic reader BRD4 and the methyltransferase G9a repress a TFEB/TFE3/MITF-independent transcriptional program that promotes autophagy and lysosome biogenesis. We show that BRD4 knockdown induces autophagy in vitro and in vivo in response to some, but not all, situations. In the case of starvation, a signaling cascade involving AMPK and histone deacetylase SIRT1 displaces chromatin-bound BRD4, instigating autophagy gene activation and cell survival. Importantly, this program is directed independently and also reciprocally to the growth-promoting properties of BRD4 and is potently repressed by BRD4-NUT, a driver of NUT midline carcinoma. These findings therefore identify a distinct and selective mechanism of autophagy regulation.
2017-05-18 | GSE90444 | GEO
Project description:GNE987 is a newly developed von Hippel-Lindau tumor suppressor (VHL)-based pan-BET-targeting PROTAC, which can bind to the target proteins (BET proteins, including BRD2, BRD3, and BRD4) and recruit them to the ubiquitin/proteasome system for selective degradation. In the our study, ChIP-Seq analysis was performed to explore the effect of GNE987 on osteosarcoma cells.
2024-08-08 | GSE243673 | GEO
Project description:BRD4 inhibitor GNE987 exerts anti-cancer effects in Osteosarcoma
| PRJNA1019364 | ENA
Project description:Osteosarcoma is the third most common cancer in adolescence and the first common primary malignant tumor of bone. The long-term prognosis of osteosarcoma, especially for unresectable and metastatic tumors, still remains unsatisfactory in the past decades. In this study, we systematically investigated the antitumor effect of imperatorin (IMP), a small molecule extracted from Angelica dahurica, in human osteosarcoma cells. The results showed that IMP triggered time-dependent and dose-dependent inhibition of tumor growth mainly by inducing autophagy promotion and G0/G1 phase arrest in vitro and in vivo. Besides, IMP treatment elevated the expression level of PTEN and p21, down-regulated the phosphorylation of AKT and mTOR. In contrast, the inhibition of PTEN using Bpv (HOpic), a potential and selective inhibitor of PTEN, concurrently rescued IMP-induced autophagy promotion, cell cycle arrest and inactivation of PTEN-PI3K-AKT-mTOR/p21 pathway. Taken together, our data revealed that imperatorin induced autophagy and cell cycle arrest through PTEN-PI3K-AKT-mTOR/p21 signaling pathway by targeting and up-regulating PTEN in human osteosarcoma cells. Hence, imperatorin is a desirable candidate for clinical treatments of osteosarcoma.
2021-12-23 | GSE180321 | GEO
Project description:Brd4 is the best characterized member of the bromo- and extra-terminal (BET) domain family of proteins and has been widely studied in tumor-associated transcriptional programs. Here we show that activation of Brd4 is associated with the presence of autophagy in NPMc+ and MLL AML cells. Brd4 binds to the promoters of Atg 3, 7 and CEBPb, and expression of these genes is markedly reduced by inhibitors of Brd4, as well as by Brd4-shRNA and CEBPb depletion. Inhibitors of Brd4 also dramatically suppress the transcription of Keap1, thereby increasing the expression of anti-oxidant genes through the Nrf2 pathway. We conclude that Brd4 plays a significant role in autophagy activation through the direct transcriptional regulation of genes essential for autophagy, as well as through the Keap1-Nrf2 axis in NPMc+ and MLL-fusion AML cells.
2017-10-11 | GSE104745 | GEO
Project description:Abstract Background: YSCH-01, a recombinant L-IFN adenovirus injection, is an oncolytic virus- based anticancer drug with dual anti-tumor effects. In previous studies, we have confirmed the potential of YSCH-01 in the treatment of malignant gliomas. Additionally, YSCH-01 has emerged as a promising candidate for osteosarcoma treatment, exhibiting significant antitumor properties. However, its specific role in osteosarcoma and the underlying mechanisms remain poorly understood. Methods: We evaluated the infectivity and efficacy of YSCH-01 in osteosarcoma cells by collecting clinical samples of osteosarcoma and conducting experiments using osteosarcoma cell lines both in vitro and in vivo. Additionally, we studies the impact of YSCH-01 on interferon overexpression at the RNA and protein levels to highlight its potential antitumor properties. Furthermore, RNA-seq analysis of tumor samples treated with YSCH-01 provided valuable insights into the altered gene expression profiles and signaling pathways, helping to elucidate the molecular basis of its antitumor effects. Results: Our findings demonstrated the dose-dependent infectivity of YSCH-01 in osteosarcoma cells, with varying effects observed across different cell lines. Both in vitro and in vivo studies showed that YSCH-01 effectively inhibited osteosarcoma cell proliferation. In CDX and PDX animal models, YSCH-01 exhibited potent therapeutic effects, particularly in terms of its distant effects. Additionally, IFN-αsignaling pathway was activated in the tumor tissues with YSCH-01 treatment. Conclusions: The initial findings of this study revealed the complex molecular pathways through which YSCH-01 exerts its antitumor effects in osteosarcoma. By elucidating the correlation between key molecular markers in osteosarcoma and patient outcomes, we have identified potential therapeutic targets, presenting a promising avenue for osteosarcoma treatment. Keywords: Osteosarcoma; Oncolytic Virus; YSCH-01; L-IFN.
2025-08-19 | GSE294206 | GEO
Project description:To investigate the mechanism that drives dramatic mistargeting of active chromatin in NUT midline carcinoma, we have identified protein interactions unique to the BRD4-NUT fusion oncoprotein compared to wild type BRD4. Using crosslinking, affinity purification, and mass spectrometry, we identified the EP300 acetyltransferase as uniquely associated with BRD4 through the NUT fusion in both NMC and non-NMC cell types. We also discovered ZNF532 among a small number of candidates associated with BRD4-NUT in NMC patient cells but not present in 293T cells.
2017-04-05 | PXD005786 | Pride