Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA296391 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Oncogenic activation of the RNA binding protein RDBP and c-Myc signaling in hepatocellular carcinoma
| PRJNA362884 | ENA
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
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.
2015-09-23 | GSE73219 | GEO
Project description:To identify proteomic signatures associated with hepatocellular carcinoma driven by MYC overexpression, proteomics was performed on the LAP-tTA/tetO-MYC mouse conditional liver cancer model. Upon MYC activation, mice form liver cancer. Differential proteomics was performed in "MYC on" (MYC-HCC) mouse liver tumors versus mouse control normal liver tissue (where MYC was not overexpressed to drive tumorigenesis -- "MYC off").
2022-10-12 | PXD031478 | Pride
Project description:Epigenetic gene regulation in various oncogenic pathways is currently an important focus of cancer research. The PI3K pathway plays a pivotal role in hepatocellular carcinoma, but the significance of histone modification in the PI3K pathway-dependent hepatotumorigenesis remains unknown. We used microarrays to investigate the oncogenic gene regulation by histone demethylase Kdm3a under PI3K signaling activation in the liver.
2017-04-01 | GSE87765 | GEO
Project description:Delineation of EZH2 oncogenic functions in hepatocellular carcinoma
| PRJNA118385 | ENA
Project description:Delineation of AR oncogenic functions in hepatocellular carcinoma
| PRJNA135817 | ENA
Project description:Massive studies have been applied in exploring the factors driving pathogenesis, progression and metastasis of hepatocellular carcinoma. However these studies were inefficient in disclosing the fundamental mechanism which promotes hepatocellular carcinoma. Zinc and zinc-finger proteins have been important in extensive biological processes for human. Supervised machine learning using bootstrapping algorithm on GEO and TCGA transcriptome data for hepatocellular carcinoma identified zinc-finger like protein ZFPL1 as potential hepatocellular carcinoma driver. Further studies validated ZFPL1 significantly promoted progression and metastasis of hepatocellular carcinoma. We performed RNA-seq on si-ZFPL1 xenograft tissue and identified CLDN3 as potential target gene for ZFPL1. Further experiments confirmed interaction between ZFPL1 and WNT signaling pathway markers. Conclusively, these studies indicated the effect and mechanism of ZFPL1 on promoting progression and metastasis of hepatocellular carcinoma and might gap the bridge between zinc-finger like proteins and hepatocellular carcinoma.
2024-10-19 | GSE277010 | GEO
Project description:Emerging evidence suggests that dysregulated RNA-binding proteins (RBPs) are associated a variety of cancers. However, the exact roles of RNA-binding proteins during the tumorigenesis of hepatocellular carcinoma (HCC) remain largely unknown. Here, we systematically searched for RBP candidates with potential oncogenic functions in HCC through multi-omics data integration strategies and identified that GPATCH4 gene is amplified and its high expression predicts a poor prognosis. We mapped the in vivo RNA binding sites of GPATCH4 by iCLIP-seq and characterized that GPATCH4 mainly bound rRNAs with a GC-rich consensus sequence. GPATCH4 promoted HCC cell proliferation and transformation both in vitro and in vivo through increasing rRNA transcription and global protein synthesis.
2025-05-30 | GSE270046 | GEO
Project description:Chromosomal rearrangement-mediated oncofusion proteins are major oncogenic drivers, with high prevalence in pediatric cancers, which often have a poor prognosis. Liquid-like condensate formation has been reported in many oncofusion proteins, supporting their oncogenic signaling and transcriptional regulation. In this study, we report that RNA-mediated nuclear condensate formation plays an essential role in supporting the oncogenic transcription of TFE3 oncofusion proteins in MiT family translocation renal cell carcinoma (tRCC), which often occurs in children and adolescents and is considered an orphan disease in RCC lacking effective treatment. The RNA binding features in the fusion partners of transcription factor E3 (TFE3) support the nuclear condensate formation of TFE3 oncofusion proteins on the chromatin, thereby enabling RNA polymerase II (RNAPII) and other RNA binding proteins, e.g., paraspeckle component 1 (PSPC1), to co-condensate and form a transcriptional hub to support oncogenic transcription in tRCC. Perturbing TFE3 oncofusion condensate formation using a nanobody fused with maltose-binding protein (MBP) approach significantly suppresses tRCC cell growth in vitro and in vivo. In summary, our data highlight the pivotal role of RNA and RNA binding proteins in supporting the liquid-like condensate formation of oncofusion proteins and in promoting oncogenic transcription.
2025-09-05 | PXD056977 | Pride