Wild-type KRAS activation drives evasion of interferon-mediated immunity and resistance to immunotherapy in hepatocellular carcinoma
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Hepatocyte, Liver
DISEASE(S): Liver Cancer
SUBMITTER: 
MANG LENG LEI
LAB HEAD: Terence Lee
PROVIDER: PXD058362 | Pride | 2025-09-18
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| CMYC_27_DDA.mzML | Mzml | |||
| CMYC_27_DIA.mzML | Mzml | |||
| CMYC_28_DDA.mzML | Mzml | |||
| CMYC_28_DIA.mzML | Mzml | |||
| CMYC_29_DDA.mzML | Mzml |
Items per page: 5 1 - 5 of 30 |
Similar Datasets
Project description:In mammalian cells, the Myc oncoprotein binds to thousands of promoters. During mitogenic stimulation of primary lymphocytes, Myc promotes an increase in expression of virtually all genes. In contrast, Myc-driven tumour cells differ from normal cells in expression of specific sets of up- and downregulated genes that have significant prognostic value. To understand this discrepancy, we studied the consequences of inducible expression and depletion of Myc in human cells and murine tumour models. Changes in Myc levels activate and repress specific sets of direct target genes that are characteristic of Myc-transformed tumour cells. Three factors account for this specificity: First, the magnitude of response parallels the change in occupancy by Myc at each promoter. Functionally distinct classes of target genes differ in the E-box sequence bound by Myc, arguing that different cellular responses to physiological and oncogenic Myc levels are controlled by promoter affinity. Secondly, Myc both positively and negatively affects transcription initiation independent of its effect on transcriptional elongation. Third, complex formation with Miz1 mediates repression of multiple target genes by Myc and the ratio of Myc and Miz1 bound to each promoter correlates with the direction of response. Myc, Miz1 and RNA polymerase II ChIPseq as well as RNAseq experiments in two human cancer cell lines and murine carcinoma cells as well as fibroblasts from Miz1M-bM-^HM-^FPOZ mice. All sequencing experiment were performed on an Illumina Genome Analyzer IIx.
2014-07-10 | E-GEOD-44672 | biostudies-arrayexpress
Project description:Overexpression of human epidermal growth factor receptor 2 (HER-2) occurs in 20% of all breast cancer subtypes, those that present the worst prognostic outcome through a very invasive and aggressive tumour. HCC-1954 (HER-2+) is a highly invasive, metastatic cell line whereas MCF-7 is mildly aggressive and non-invasive. We investigated membrane proteins from both cell lines that could have a pivotal biological significance in the metastatic process. Membrane protein enrichment for HCC-1954 and MCF-7 proteomic analysis was performed. The samples were analysed on a two-dimensional liquid chromatography coupled to mass spectrometry (2-D-SCX/RP-LCMS system) and the protein expression was quantified by MSE method. High abundance membrane proteins were confirmed by western blot, immunofluorescence, and flow cytometry. Protein interaction prediction and correlations with TCGA patient’s data were conducted by bioinformatic analysis. The comparison between HCC-1954 and MCF-7 membrane proteins revealed that proteins involved in cytoskeleton organization, such as HER-2, β-1 integrin, E-cadherin and CD166 (ALCAM) were more abundant in HCC-1954. The Cancer Genome Atlas (TCGA) analysis showed a trend toward a positive correlation between HER-2 and β-1 integrin in HER-2+ breast cancer patients. Differences in protein profile and abundance reflect distinctive capabilities for motility and invasiveness between cell lines. HCC-1954 could be an excellent model to study β1 integrin and epithelial–mesenchymal transition (EMT) involvement in trastuzumab resistance mechanisms.
2022-10-14 | PXD023876 | Pride
Project description:Peptides of HCC cell lines and tumour tissues were fractionated by Hp-RP to eight fractions and repeated analysed three times by the LC-MS/MS detection system consisted of the EASY-nLC 1000 coupled to the Q-Exactive HF mass spectrometer using data dependent acquisition mode.
2022-11-11 | PXD035028 | Pride
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:MicroRNAs (miRNAs) are abundant in the circulation and play a central role in diverse biological processes; they may be useful for early diagnosis of hepatocellular carcinoma (HCC). We conducted a two-phase, case-control study (20 pairs for the discovery set and 49 pairs for the validation set) to test the hypothesis that genome-wide dysregulation of circulating miRNAs differentiate HCC cases from controls. Taqman low density arrays were used to examine genome-wide miRNA expression for the discovery set, and quantitative RT-PCR was used to validate candidate miRNAs for both discovery and validation sets. Sixty-six miRNAs were found to be significantly over-expressed in plasma of HCC cases compared to controls after adjusting for false discovery rate (p<0.05). A volcano plot indicated that 7 miRNAs had greater than 2-fold case-control differences with p<0.01. Four significant miRNAs (miR-150, miR-30c, miR-483-5p and miR-520b) detectable in all samples with varied expression levels were further validated in a validation set. MiR-483-5p was statistically significantly over-expressed in HCC cases compared with controls (3.20 vs. 0.82, p<0.0001). HCC risk factors and clinic-pathological characteristics did not influence miR-483-5p expression. The combination of plasma miR-483-5p level and HCV status can significantly differentiate HCC cases from controls with an AUC of 0.908 (p<0.0001). The sensitivity and specificity were, respectively, 75.5% and 89.8%. These preliminary results suggest the importance of dysregulated circulating miR-483-5p as a potential HCC biomarker. Confirmation of aberrant expression of miR-483-5p in a large prospective HCC study will provide support for its application to HCC detection. A hospital-based HCC case-control study including 20 HCC patients and 20 controls is conducted in Columbia University Medical Center (CUMC), which is approved by the Institutional Review Board. Cases were newly diagnosed HCC patients who were treated in the Hepatobiliary Oncology Clinics, CUMC, and examined pathologically. Controls were recruited from volunteers through the Research Recruitment and Minority Outreach (RRMO) core of Herbert Irving Comprehensive Cancer Center (HICCC). Flyers were placed at strategic locations around CUMC where hospital visitors and employees frequent or were handed out at inreach events at the hospital or at outreach events in the community. Interested participants were directed to contact the trained recruitment staff from the RRMO and given further information about participation. Interested participants were excluded from the control group if diagnosed for any kind of cancer or liver disease. Eligible controls were asked to fill out the same demographic and epidemiological questionnaire as HCC cases. In the current study, controls were matched with HCC cases on age (M-BM-15 yrs), gender (male/female) and ethnicities (Caucasian/Hispanic/African-American/Asian).
2013-08-21 | E-GEOD-50013 | biostudies-arrayexpress
Project description:The Myc-Max heterodimer has been thought of as a sequence specific DNA binding protein that regulates transcription of a large number of genes. We demonstrate here that the positions of the human genome occupied by Myc-Max correlate with the RNA polymerase II (Pol II) transcription complex rather than to the canonical DNA binding sequence element CACGTG. The heterodimer is positioned slightly upstream of essentially all promoter proximal paused polymerases and is found throughout the transcribed regions of genes. Using a multi-genome analysis of promoter regions we show that the heterodimers are oriented with respect to the direction of transcription with Myc downstream of Max. In strong support of a model in which the Myc is recruited by transcription complexes rather than specific DNA sequences, we found that the difference in affinities of Myc-Max heterodimers for CACGTG versus non-specific DNA is not great enough to drive the pattern of genome occupancy exhibited. A total of 2 ChIP-Seq data for Myc and Max in human HeLa cell.
2013-01-02 | E-GEOD-43227 | 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:Global expression profiling of miRNAs in liver tissue of HBV infected HCC and chronic hepatitis B (CHB) with no fibrosis was evaluated. A total of 40 differentially expressed miRNAs were identified in HCC. Top 10 miRNAs are validated in more numbers of HCC tisuues by qRT PCR. Finally six miRNAs (miR-15a, miR-16, miR-21,miR-29b-3p, miR-126, miR-142-3p, miR-193a-5p) showed similar expression pattern in both microarray and qRT PCR Differential expression analysis of microRNAs in HBV infected HCC (n=4) compared to CHB patients with no fibrosis (n=8) as control.
2015-04-15 | E-GEOD-67882 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) poses a severe threat to human health. The NET-1 protein has been proved to be strongly associated with HCC proliferation and metastasis in our previous study. Here, we established and validated NET-1 siRNA nanoparticles system to conduct targeted gene therapy of HCC xenograft in vivo with the aid of sonodynamic therapy (SDT). Then, a label-free proteome mass spectrometry workflow to analyze formalin-fixed and paraffin-embedded HCC xenograft samples collected in this study. The result showed that 78 proteins were differentially expressed after NET-1 protein inhibited. Among them, the expression of 61 proteins up-regulated and the expression of 17 proteins were significantly down-regulated. Of the differentially expressed proteins, the vast majority of Gene Ontology enrichment terms belong to the biological process. The KEGG pathway enrichment analysis showed that the 78 differentially expressed proteins significantly enriched in 45 pathways. We concluded that the function of the NET-1 gene is not only to regulate HCC but also to participate in a variety of biochemical metabolic pathways in the human body. Furthermore, the protein-protein interaction analysis indicated that the interactions of differentially expressed proteins are incredibly sophisticated. All the protein-protein interactions happened after the NET-1 gene has been silenced. Finally, our study also provides a useful proposal for targeted therapy based on tetraspanin proteins to treat HCC, and further mechanism investigations are needed to reveal a more detailed mechanism of action for NET-1 protein regulation of HCC.
2021-09-09 | PXD020763 | Pride
Project description:MicroRNAs (miRNAs) are aberrant expressed in hepatocellular carcinoma (HCC) tissue and play a central role in diverse biological processes. We conducted a genome-wide miRNAs screening in 10 pairs of HCC tumor and adjacent non-tumor tissues to test the hypothesis that dysregulation of miRNAs in HCC tumor tissue are partially due to aberrant methylation in relevant miRNAs host genes. Taqman low density arrays were used to examine miRNA profiles in paired HCC tissues, and quantitative RT-PCR was used to validate candidate miRNAs for both discovery and validation sets. A cross-sectional study was conducted in 10 HCC tumor tissues and 10 adjacent non-tumor tissues in Columbia University Medical Center (CUMC), which is approved by the Institutional Review Board.
2014-02-08 | E-GEOD-54751 | biostudies-arrayexpress