Project description:HepG2 cell lines were treated with TCDD, as an activator for the TF AhR/arnt since it is a known ligand for AhR. Hepatocellular carcinoma (HCC) is a fatal disease with currently very limited beneficial therapies. MicroRNAs (miRs), which are considered to be master regulators of gene expression, have significant influence on cellular pathways and phenotype, and are de-regulated in HCC, and hence are thought to be of great therapeutic potential as novel targets. We identified hsa-miR-191 as a potential target for HCC therapy. Inhibition of this miR causes decreased cell proliferation and induction of apoptosis in vitro as well as a significant reduction of tumor mass in vivo in an orthotopic liver xenograft model. This miR was also found to be up-regulated by a dioxin, a known liver carcinogen, and was found to be a key regulator of cancer related pathways. HCC cell lines treated with TCDD and control. Although this experiment was done with dual channel, chanels are not compared, irrelevant samples were on the reciprocal channel. Sample data tables represent relevant, single channel data.
Project description:Chronic infections by hepatitis B virus (HBV) and hepatitis C virus (HCV) appear to be the most significant causes of hepatocellular carcinoma (HCC). Aberrant promoter methylation is known to be deeply involved in cancer, including HCC. In this study, we analyzed aberrant promoter methylation on genome-wide scale in 6 HCCs including 3 HBV-related and 3 HCV-related HCCs, 6 matched noncancerous liver tissues and 3 normal liver tissues by methylated DNA immunoprecipitation-on-chip analysis. Candidate genes with promoter methylation were detected more frequently in HCV-related HCC. Candidate genes methylated preferentially to HBV-related or HCV-related HCCs were detected and selected, and methylation levels of the selected genes were validated using 125 liver tissue samples, including 61 HCCs (28 HBV-related HCCs and 33 HCV-related HCCs) and matched 59 matched noncancerous livers, and 5 normal livers, by quantitative methylation analysis using MALDI-TOF mass spectrometry. Among analyzed genes, preferential methylation in HBV-related HCC was validated in 1 gene only. However, 15 genes were found methylated preferentially in HCV-related HCC, which was independent from age. Hierarchical clustering of HCC using these 15 genes stratified HCV-related HCC as a cluster of frequently methylated samples. The 15 genes included genes inhibitory to cancer-related signaling such as RAS/RAF/ERK and Wnt/b-catenin pathways. It was indicated that genes methylated preferentially in HCV-related HCC exist, and it was suggested that DNA methylation might play an important role in HCV-related HCC by silencing cancer-related pathway inhibitors. we analyzed aberrant promoter methylation in 6 HCC clinical samples (including 3 HBV-related HCCs and 3 HCV-related HCCs) and their matched noncancerous tissues on genome-wide scale by the method. Candidate regions of promoter methylation preferentially to HBV-related HCC and HCV-related HCC were selected, and the methylation levels of these genes were measured quantitatively using MALDI-TOF mass spectrometry. Expression levels of these 6 pairs of HCC and 4 more pairs of HCCs and surrounding noncancerous tissues were analyzed by expression array and are reported in this Series. <br><br>This experiment was reloaded in November 2010 after additional curation. this dataset is part of the TransQST collection.
Project description:The goal of this experiment was to study the effectivity of miR down regulation by using an anti-miR molecule. Hepatocellular carcinoma (HCC) is a fatal disease with currently very limited beneficial therapies. MicroRNAs (miRs), which are considered to be master regulators of gene expression, have significant influence on cellular pathways and phenotype, and are de-regulated in HCC, and hence are thought to be of great therapeutic potential as novel targets. We identified hsa-miR-191 as a potential target for HCC therapy. Inhibition of this miR causes decreased cell proliferation and induction of apoptosis in vitro as well as a significant reduction of tumor mass in vivo in an orthotopic liver xenograft model. This miR was also found to be up-regulated by a dioxin, a known liver carcinogen, and was found to be a key regulator of cancer related pathways. HCC cell line treated with anti-miR-191, and treated with negative control anti-miR. Although this experiment was done with dual channel, chanels are not compared, irrelevant samples were on the reciprocal channel. Sample data tables represent relevant, single channel data.
Project description:Formalin-fixed paraffin-embedded (FFPE) tissues are crucial clinical archives linked with long-term follow-up data, yet the suitability of deep proteomic analysis on samples stored over 30 years remains largely unexplored. This study aimed to verify the feasibility of deep proteomic analysis on extremely long-term stored FFPE samples. We employed adaptive focused acoustics (AFA) technology for efficient protein extraction, combined with SP3 cleanup and data-independent acquisition (DIA) mass spectrometry using a ZenoTOF 7600, to analyze FFPE samples of hepatocellular carcinoma (HCC) and adjacent non-tumor liver (NTL) tissues from 19 HCC patients from 1988-1992.
Project description:A recent study by Castelo-Branco, P., et al. Methylation of the TERT promoter and risk stratification of childhood brain tumours: an integrative genomic and molecular study. Lancet Oncol 2013;14:534-542 found upstream of the transcription start site (UTSS) hypermethylation of TERT is associated with tumor progression and poor prognosis in paediatric brain tumours. They interpreted that the UTSS region of telomerase reverse transcriptase (TERT) gene is a potentially accessible biomarker for various cancers. This study, we aimed to explore the role of TERT in hepatocellular carcinoma (HCC) and to investigate whether the UTSS region of TERT promoter shows the same methylation pattern in HCC. We analyzed a methylation assay of TERT including the UTSS region in 125 paired HCC samples using Mass Array EpiTyper (Sequenom, SanDiego, CA, USA). To obtain the relationship between TERT promoter methylation status and TERT expression level, we analysed a validation group of 12 paired HCC samples and acquired the FPKM value of TERT gene.
Project description:We integrated the copy number data with gene expression data from the same HCC samples, and identified fifteen putative driver genes with recurrently genomic aberrations and their associated modules in HCC. We further confirmed empirically that three putative driver genes (MYH10, CEP104 and RRS1) play significant roles in tumor initiation and progression of HCC. Notably, we demonstrated that RRS1 regulates the MDM2-P53 pathway and promotes tumor progression by retaining RPL11 in the nucleolus in HCC. Altogether, these data provide insights into novel cancer driver genes and suggested molecular targets for treatment for HCC.
Project description:We integrated the copy number data with gene expression data from the same HCC samples, and identified fifteen putative driver genes with recurrently genomic aberrations and their associated modules in HCC. We further confirmed empirically that three putative driver genes (MYH10, CEP104 and RRS1) play significant roles in tumor initiation and progression of HCC. Notably, we demonstrated that RRS1 regulates the MDM2-P53 pathway and promotes tumor progression by retaining RPL11 in the nucleolus in HCC. Altogether, these data provide insights into novel cancer driver genes and suggested molecular targets for treatment for HCC.
Project description:We integrated the copy number data with gene expression data from the same HCC samples, and identified fifteen putative driver genes with recurrently genomic aberrations and their associated modules in HCC. We further confirmed empirically that three putative driver genes (MYH10, CEP104 and RRS1) play significant roles in tumor initiation and progression of HCC. Notably, we demonstrated that RRS1 regulates the MDM2-P53 pathway and promotes tumor progression by retaining RPL11 in the nucleolus in HCC. Altogether, these data provide insights into novel cancer driver genes and suggested molecular targets for treatment for HCC.
Project description:We integrated the copy number data with gene expression data from the same HCC samples, and identified fifteen putative driver genes with recurrently genomic aberrations and their associated modules in HCC. We further confirmed empirically that three putative driver genes (MYH10, CEP104 and RRS1) play significant roles in tumor initiation and progression of HCC. Notably, we demonstrated that RRS1 regulates the MDM2-P53 pathway and promotes tumor progression by retaining RPL11 in the nucleolus in HCC. Altogether, these data provide insights into novel cancer driver genes and suggested molecular targets for treatment for HCC.