Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1186337 | ENA |
REPOSITORIES: ENA
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Project description:Hepatocellular carcinoma (HCC) is a formidable malignancy with limited effective therapeutic avenues. This study was designed to investigate the role of transglutaminase 2 (TGM2) in promoting HCC progression and assess its potential as a target for therapeutic intervention in HCC treatment.TMG2 expression was positively related to a higher AFP level, poor differentiation, and a later BCLC stage. Tgm2 deficiency or H3Q5ser inhibition notably restrained HCC progression. Mechanism research revealed that TGM2-mediated H3Q5ser modifications promote HCC progression via MYC pathway signaling. Furthermore, transcriptional intermediary factor 1 beta (TIF1-β/TRIM28) mediated the recruitment of TGM2 by MYC to facilitate H3Q5ser modifications on MYC targets. Finally, targeting the TGM2 transglutaminase activity significantly suppressed HCC progression in preclinical models.
2024-12-16 | GSE283279 | GEO
Project description:Hepatocellular carcinoma (HCC) is a formidable malignancy with limited effective therapeutic avenues. This study was designed to investigate the role of transglutaminase 2 (TGM2) in promoting HCC progression and assess its potential as a target for therapeutic intervention in HCC treatment.TMG2 expression was positively related to a higher AFP level, poor differentiation, and a later BCLC stage. Tgm2 deficiency or H3Q5ser inhibition notably restrained HCC progression. Mechanism research revealed that TGM2-mediated H3Q5ser modifications promote HCC progression via MYC pathway signaling. Furthermore, transcriptional intermediary factor 1 beta (TIF1-β/TRIM28) mediated the recruitment of TGM2 by MYC to facilitate H3Q5ser modifications on MYC targets. Finally, targeting the TGM2 transglutaminase activity significantly suppressed HCC progression in preclinical models.
2024-12-16 | GSE283278 | GEO
Project description:Bidirectional communication between tumors and neurons has emerged as a key facet of the tumor microenvironment that drives malignancy. Another hallmark feature of cancer is epigenomic dysregulation, where alterations in gene expression influences cell states and interactions with the tumor microenvironment. Using the pediatric brain tumor ependymoma (EPN) as a model, we found that inhibition of histone serotonylation blocks EPN tumorigenesis and regulates expression of a core set of developmental transcription factors (TFs). High-throughput, in vivo screening of these TFs revealed that ETV5 promotes EPN tumorigenesis and functions by enhancing repressive chromatin states. Neuropeptide Y (NPY) is amongst the genes repressed by ETV5 and its overexpression suppresses EPN tumor progression and tumor-associated network hyperactivity via synaptic remodeling. Collectively, these studies identify histone serotonylation as a key driver of EPN tumorigenesis, while further revealing how neuronal signaling, neuro-epigenomics, and developmental programs are intertwined to drive malignancy in brain cancer.
2024-09-09 | PXD048170 | Pride
Project description:We identified a novel mechanism by which IL-6/STAT3 signaling up-regulates CD133 expression and promotes HCC progression. STAT3 activation upregulates the expression of CD133 during liver carcinogenesis. Targeting STAT3-mediated CD133 overexpression may represent a promising therapeutic strategy for HCC patients via eradicating the liver tumor microenviornment. To develop novel cancer therapeutic strategies by identification of signaling pathways or biomarkers and understanding their functions on cancer stem cell biology, we determined CD133 expression and STAT3 activation with tumor microenvironment in HCC patient tissues. The relation of STAT3 activation and CD133 expression was investigated by luciferase assay, shRNA knock-down, and chromatin immunoprecipitation assay in HCC cells, and in vivo xenograft model.
2014-08-08 | E-GEOD-60194 | biostudies-arrayexpress
Project description:We identified a novel mechanism by which IL-6/STAT3 signaling up-regulates CD133 expression and promotes HCC progression. STAT3 activation upregulates the expression of CD133 during liver carcinogenesis. Targeting STAT3-mediated CD133 overexpression may represent a promising therapeutic strategy for HCC patients via eradicating the liver tumor microenviornment.
2014-08-08 | GSE60194 | GEO
Project description:The orphan nuclear receptor NR2E3 (Nuclear receptor subfamily 2 group E, Member 3) is an epigenetic player essential for p53 activation during liver injuries through its modulation of chromatin accessibility. Nonetheless, a precise tumor suppressive and epigenetic role of NR2E3 in hepatocellular carcinoma (HCC) remains unclear. HCC patients expressing low NR2E3 exhibit unfavorable clinical outcomes, aligning with heightened activation of the WNT/β-catenin signaling pathway. The murine HCC models utilizing NR2E3 knockout mice consistently exhibits accelerated liver tumor formation and progression accompanied by enhanced activation of WNT/β-catenin signaling pathway and inactivation of p53 signaling pathway. At cellular level, the loss of NR2E3 increases the acquisition of aggressive cancer cell phenotype and tumorigenicity and upregulates key genes in the WNT/β-catenin pathway with enhanced chromatin accessibility. This event is mediated through increased formation of active transcription complex involving Sp1, β-catenin, and p300, a histone acetyltransferase, on the promoters of target genes. These findings demonstrate that the loss of NR2E3 promotes WNT/β-catenin signaling activation at cellular, organismal, and clinical levels. In summary, NR2E3 is a novel tumor suppressor that maintains epigenetic homeostasis, thereby preventing activation of WNT/β-catenin signaling that promotes HCC formation and progression.
2024-08-26 | GSE243020 | GEO
Project description:METTL3 mediated m6A mRNA modification promotes esophageal cancer initiation and progression via Notch signaling pathway
| PRJNA743037 | ENA
Project description:Epigenetic alterations appear to modulate Myc signaling. We investigated the role of the histone demethylase JMJD2B in Myc-mediated neuroblastoma pathogenesis. We demonstrate that Myc physically interacts with and recruits this epigenetic modifier, which removes repressive H3K9 methyl marks from Myc-target genes. JMJD2B regulates neuroblastoma proliferation and, together with MYCN amplification, identifies a subgroup of poor prognosis patients. We identify a novel histone demethylase inhibitor, ciclopirox, which targets JMJD2B and, consequently, Myc signaling, thereby inhibiting neuroblastoma proliferation and inducing differentiation. In xenograft studies, genetic and pharmacologic inhibition of JMJD2B resulted in significant tumor growth restriction. Our findings provide insight into epigenetic regulation of Myc via histone methylation and proof-of-concept for pharmacologic inhibition of histone demethylases to target Myc signaling in cancer. 8 samples were treated with vehicle or ciclopirox.
2014-01-01 | E-GEOD-45969 | biostudies-arrayexpress
Project description:Epigenetic alterations appear to modulate Myc signaling. We investigated the role of the histone demethylase JMJD2B in Myc-mediated neuroblastoma pathogenesis. We demonstrate that Myc physically interacts with and recruits this epigenetic modifier, which removes repressive H3K9 methyl marks from Myc-target genes. JMJD2B regulates neuroblastoma proliferation and, together with MYCN amplification, identifies a subgroup of poor prognosis patients. We identify a novel histone demethylase inhibitor, ciclopirox, which targets JMJD2B and, consequently, Myc signaling, thereby inhibiting neuroblastoma proliferation and inducing differentiation. In xenograft studies, genetic and pharmacologic inhibition of JMJD2B resulted in significant tumor growth restriction. Our findings provide insight into epigenetic regulation of Myc via histone methylation and proof-of-concept for pharmacologic inhibition of histone demethylases to target Myc signaling in cancer. 8 samples were transfected with two different siRNAs for control, JMJD2B, MYCN and JARID1A.
2014-01-01 | E-GEOD-45967 | biostudies-arrayexpress
Project description:Global transcriptomic alterations of both coding and non-coding RNA species are a ubiquitous feature associated with human cancers including hepatocellular carcinoma (HCC). Dysregulation of RNA-binding proteins (RBPs), the key regulators of RNA processing, is one mechanism in which cancer cells select to promote tumorigenesis. We analyzed genomic alterations amongst a family of more than 800 mRNA RBPs (mRBPs) in 1,225 clinical specimens from HCC patients and found that RBPs are significantly activated through gene amplification in a subset of tumors with poor prognosis, suggesting their potential oncogenic roles in HCC progression. Amongst the top candidates, RD binding protein (RDBP) was further characterized for its oncogenic role and effects on the HCC transcriptome. While the activation of RDBP induced an oncogenic phenotype, the abrogation of RDBP in HCC cells significantly decreased cancer associated phenotypes such as cell proliferation, migration/invasion and tumorigenicity in vivo. Further microarray analyses revealed that RDBP-dependent genes were tumor-related with a significant enrichment for c-Myc targets, suggesting interplay between RDBP and c-Myc signaling. Similar data were also found in HCC clinical specimens where c-Myc amplification was uncommon. Consistently, the RDBP-dependent c-Myc target gene signature was able to predict HCC patient survival in two independent cohorts of more than 400 patients. Taken together, our results suggest that oncogenic activation of RDBP is a novel mechanism that contributes to global transcriptome imbalance that is selective for the activation of c-Myc oncogenic signaling in HCC. We used microarray analysis to determine the affects of siRNA mediated RDBP knockdown in HCC transcriptome in cell lines. Hep3b and Huh1 cells were transfected with RDBP or scramble control siRNA for 48 hours in quadruplicates. Quality control using Spearman or Pearson correlation removes outliers resulting in triplicates for each group
2015-09-23 | E-GEOD-73219 | biostudies-arrayexpress