Project description:Tumor interferon signaling regulates the expression of immunosuppressive molecules and promotes cancer immune evasion. Although the role of long noncoding RNAs (lncRNAs) in the regulation of gene expression is now emerging, their function in tumor interferon signaling remains unexplored. We have identified the interferon-γ (IFNγ)-stimulated non-coding RNA 1 (INCA1) as a novel lncRNA expressed form the PD-L1 locus. INCA1 is expressed in multiple tumor types and its levels increase after IFNγ stimulation. Silencing INCA1 decreased the expression of several interferon-stimulated genes (ISGs). We discovered that the transcripts of some ISGs are negatively regulated by HNRNPH1. We demonstrate that binding of INCA1 to HNRNPH1 is required for ISG expression. Overall, our findings reveal a mechanism of tumor interferon signaling regulation mediated by the lncRNA INCA1.
Project description:Tumor interferon signaling regulates the expression of immunosuppressive molecules and promotes cancer immune evasion. Although the role of long noncoding RNAs (lncRNAs) in the regulation of gene expression is now emerging, their function in tumor interferon signaling remains unexplored. We have identified the interferon-γ (IFNγ)-stimulated non-coding RNA 1 (INCA1) as a novel lncRNA expressed form the PD-L1 locus. INCA1 is expressed in multiple tumor types and its levels increase after IFNγ stimulation. In this study we performed transcriptome analysis (RNA-seq) of INCA1 knockdown cells and show that INCA1 regulates the expression of several interferon-stimulated genes. Overall, our findings reveal INCA1 as a critical component of the tumor interferon signaling.
Project description:1. Evaluate the diagnostic value of long noncoding RNA (CCAT1) expression by RT-PCR in peripheral blood in colorectal cancer patients versus normal healthy control personal.
2. Evaluate the clinical utility of detecting long noncoding RNA (CCAT1) expression in diagnosis of colorectal cancer patients & its relation to tumor staging.
3. Evaluate the clinical utility of detecting long noncoding RNA (CCAT1) expression in precancerous colorectal diseases.
4. Compare long noncoding RNA (CCAT1) expression with traditional marker; carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA19-9) in diagnosis of colorectal cancer.
Project description:Long noncoding RNAs (lncRNAs) are key regulators of gene expression both in physiological and pathological conditions. Previous studies showed changes in lncRNA expression during tumorigenesis. To analyze the role of lncRNAs in tumor interferon signaling and cancer-mediated immunosuppression, we used RNA-seq technique to identify lncRNAs that are differentially expressed in GBM patient-derived cells stimulated with interferon gamma compared to unstimulated cells. 15,768 lncRNAs were surveyed in the analysis. RNA-seq data show upregulation of 113 lncRNAs upon interferon gamma treatment (p value < 0.01, fold change > 2). Our findings indicate that the expression of several lncRNAs is stimulated by interferon gamma suggesting a critical role of lncRNAs in tumor interferon signaling.
Project description:Long noncoding RNAs (lncRNAs) have appeared to be involved in the most diverse cellular processes through multiple mechanisms. Here we describe a previously uncharacterized human lncRNA, CONCR (cohesion regulator noncoding RNA), transcriptionally activated by MYC, which is upregulated in multiple cancer types. The expression of CONCR is cell cycle-regulated, and it is required for cell cycle progression and DNA replication. Moreover, cells depleted of CONCR show severe defects in sister chromatid cohesion, suggesting an essential role for CONCR in cohesion establishment during cell division. CONCR interacts with and regulates the activity of DDX11, a DNA-dependent ATPase and helicase involved in DNA replication. These findings suggest a novel mechanism of action for CONCR in the modulation of DDX11 enzymatic activity, unveiling the direct involvement of a lncRNA in the establishment of sister chromatid cohesion. Characterization of the function of the long noncoding RNA CONCR. A549 were transfected with a control siRNA or with a combination of two siRNAs targeting CONCR. Three independent siRNA-mediated knockdowns (siRNA CONCR REP1, 2 and 3) and controls (siRNA Control REP1, 2 and 3) were used for the analysis.
Project description:Long noncoding RNAs (lncRNAs) have appeared to be involved in the most diverse cellular processes through multiple mechanisms. Here we describe a previously uncharacterized human lncRNA, CONCR (cohesion regulator noncoding RNA), transcriptionally activated by MYC, which is upregulated in multiple cancer types. The expression of CONCR is cell cycle-regulated, and it is required for cell cycle progression and DNA replication. Moreover, cells depleted of CONCR show severe defects in sister chromatid cohesion, suggesting an essential role for CONCR in cohesion establishment during cell division. CONCR interacts with and regulates the activity of DDX11, a DNA-dependent ATPase and helicase involved in DNA replication. These findings suggest a novel mechanism of action for CONCR in the modulation of DDX11 enzymatic activity, unveiling the direct involvement of a lncRNA in the establishment of sister chromatid cohesion. Characterization of the function of the long noncoding RNA CONCR. Analysis of DDX11 chromatin binding by ChIP-seq in the presence or absence of CONCR.
Project description:Long noncoding RNAs (lncRNAs) have appeared to be involved in the most diverse cellular processes through multiple mechanisms. Here we describe a previously uncharacterized human lncRNA, CONCR (cohesion regulator noncoding RNA), transcriptionally activated by MYC, which is upregulated in multiple cancer types. The expression of CONCR is cell cycle-regulated, and it is required for cell cycle progression and DNA replication. Moreover, cells depleted of CONCR show severe defects in sister chromatid cohesion, suggesting an essential role for CONCR in cohesion establishment during cell division. CONCR interacts with and regulates the activity of DDX11, a DNA-dependent ATPase and helicase involved in DNA replication. These findings suggest a novel mechanism of action for CONCR in the modulation of DDX11 enzymatic activity, unveiling the direct involvement of a lncRNA in the establishment of sister chromatid cohesion. Characterization of the function of the long noncoding RNA CONCR. HCT116 p53-/- cells were left untreated (0h) or treated with the DNA damaging drug 5-FU for 4h and 12h.