Expression data from CSC and Non-CSC of three primary HCC samples
Ontology highlight
ABSTRACT: Hepatocellular carcinoma (HCC) represents the major subtype of liver cancer, characterized with a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may account for a hierarchical organization of heterogeneous cancer cells. However, how liver CSCs sustain their self-renewal remains largely unknown. We used microarrays to discover the long non-coding RNAs (lncRNAs) expression underlying cell stem cell (CSC) and non cell stem cell (non-CSC) and identified distinct lncRNAs during this process.
Project description:Hepatocellular carcinoma (HCC) represents the major subtype of liver cancer, characterized with a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may account for a hierarchical organization of heterogeneous cancer cells. However, how liver CSCs sustain their self-renewal remains largely unknown. We used microarrays to discover the long non-coding RNAs (lncRNAs) expression underlying cell stem cell (CSC) and non cell stem cell (non-CSC) and identified distinct lncRNAs during this process. We sorted CD13+CD133+ and CD13-CD133- cells from Hep3B, Huh7, and PLC/PRF/5 HCC cell lines as liver CSCs and non-CSCs, then hybridized on Affymetrix microarrays. We sought to identify distinct lncRNAs in liver CSCs.
Project description:Hepatocellular carcinoma (HCC) represents the major subtype of liver cancer, characterized with a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may account for a hierarchical organization of heterogeneous cancer cells. However, how liver CSCs sustain their self-renewal remains largely unknown. We used microarrays to discover the long non-coding RNAs (lncRNAs) expression underlying cell stem cell (CSC) and non cell stem cell (non-CSC) and identified distinct lncRNAs during this process.
Project description:Triple Negative Breast Cancer (TNBC), the deadliest form of this disease, lacks a targeted therapy. TNBC tumors that fail to respond to chemotherapy are characterized by a repressed Interferon/Signal Transducer and Activator of Transcription (IFN/STAT) gene signature and are often enriched for Cancer Stem Cells (CSCs). We have found that human mammary epithelial cells that undergo an Epithelial-to-Mesenchymal Transition (EMT) following transformation acquire CSC properties. These mesenchymal/CSCs have a significantly repressed IFN/STAT gene expression signature and an enhanced ability to migrate and form tumor spheres. Treatment with Interferon-Beta (IFNb) led to a less aggressive epithelial/non-CSC-like state, with repressed expression of mesenchymal proteins (VIMENTIN, SLUG), reduced migration and tumor sphere formation, and re-expression of CD24 (a surface marker for non-CSCs), concomitant with an epithelial-like morphology. The CSC-like properties were correlated with high levels of unphosphorylated Interferon Stimulated Gene Factor 3 (U-ISGF3), which was previously linked to resistance to DNA damage. Inhibiting the expression of IRF9 (the DNA-binding component of U-ISGF3) reduced the migration of mesenchymal/CSCs. Here we report a positive translational role for IFNb as gene expression profiling of patient derived TNBC tumors demonstrates that an IFNb Metagene signature correlates with improved patient survival, an immune response linked with Tumor Infiltrating Lymphocytes (TILs) and a repressed CSC Metagene signature. Taken together, our findings indicate that repressed IFN signaling in TNBCs with CSC-like properties is due to high levels of U-ISGF3, and that treatment with IFNb reduces CSC properties, suggesting a novel therapeutic strategy to treat drug-resistant, highly aggressive TNBC tumors.
Project description:Abstract:
The cancer stem cell hypothesis has gained currency in recent times but concerns remain about its scientific foundations because of significant gaps that exist between research findings and comprehensive knowledge about cancer stem cells (CSCs). In this light, a mathematical model that considers hematopoietic dynamics in the diseased state of the bone marrow and peripheral blood is proposed and used to address findings about CSCs. The ensuing model, resulting from a modification and refinement of a recent model, develops out of the position that mathematical models of CSC development, that are few at this time, are needed to provide insightful underpinnings for biomedical findings about CSCs as the CSC idea gains traction. Accordingly, the mathematical challenges brought on by the model that mirror general challenges in dealing with nonlinear phenomena are discussed and placed in context. The proposed model describes the logical occurrence of discrete time delays, that by themselves present mathematical challenges, in the evolving cell populations under consideration. Under the challenging circumstances, the steady state properties of the model system of delay differential equations are obtained, analyzed, and the resulting mathematical predictions arising therefrom are interpreted and placed within the framework of findings regarding CSCs. Simulations of the model are carried out by considering various parameter scenarios that reflect different experimental situations involving disease evolution in human hosts.
Model analyses and simulations suggest that the emergence of the cancer stem cell population alongside other malignant cells engenders higher dimensions of complexity in the evolution of malignancy in the bone marrow and peripheral blood at the expense of healthy hematopoietic development. The model predicts the evolution of an aberrant environment in which the malignant population particularly in the bone marrow shows tendencies of reaching an uncontrollable equilibrium state. Essentially, the model shows that a structural relationship exists between CSCs and non-stem malignant cells that confers on CSCs the role of temporally enhancing and stimulating the expansion of non-stem malignant cells while also benefitting from increases in their own population and these CSCs may be the main protagonists that drive the ultimate evolution of the uncontrollable equilibrium state of such malignant cells and these may have implications for treatment.
Project description:CSCs differentially secrete the BMP antagonist Gremlin1 compared to non-stem glioma populations. Knockdown of Gremlin1 decreases CSC proliferation and tumorigenicity, establishing Gremlin1 as an essential effector for CSC maintenance. We used a microarray to determine the gene expression programs that are activated downstream of Gremlin1 that might be responsible for CSC maintenance.
Project description:CSCs differentially secrete the BMP antagonist Gremlin1 compared to non-stem glioma populations. Knockdown of Gremlin1 decreases CSC proliferation and tumorigenicity, establishing Gremlin1 as an essential effector for CSC maintenance. We used a microarray to determine the gene expression programs that are activated downstream of Gremlin1 that might be responsible for CSC maintenance. Glioma CSC cultures from two distinct patient-derived specimens (528 and 3691) were transduced with lentivirus expressing non-targeting scrambled shRNA or one of two distinct Gremlin1 shRNAs (shGrem1_485 and shGrem1_2456) for 72 hours (total of six samples). RNA was extracted for array hybridization.
Project description:To explore the target genes of long noncoding RNA lncTCF7, we established lncTCF7-silenced HCC primary CSC cells and conducted transcriptome microarray analysis. We used microarrays to identify distinct gene expression underlying shCtrl and shlncTCF7 of hepatocellular carcinoma sample stem cells. We cultured shlncTCF7 and shCtrl cells from hepatocellular carcinoma (HCC) clinical sample, then hybridized on Affymetrix microarrays. We sought to identify distinct target genes of lncTCF7 in liver cancer stem cells (CSCs).
Project description:In the present study, we have characterized the putative Cancer Stem Cell population of Oral Squamous Cell Carcinoma by various cellular and molecular assay. Subsequently we performed gene expression profiling of SCC25 cell line with CD44highCD24low(CSC) and CD44lowCD24high(Non-CSC) phenotypes using illumina BeadChip Array. Further, systematic computational analysis was performed to identify CSC-like gene signatures in the oral cancer cells. Differentially expressed genes were subjected to pathway analysis in IPA. The analysis lead to the identification of few relevant signaling pathway implicated in stemness.
Project description:Cancer stem cells (CSC) were isolated based on the putative stem cell marker CD133. This subset of cells has been shown to have superior tumorigenicity and metastatic ability compared to cells in the non-CSC compartment (i.e. CD133-). We compared microRNA expression profiles of CSCs to non-CSCs to identify disparities in miRNA expression and explore how these miRNAs may provide a selective survival advantage to cancer stem cells.