Project description:MicroRNAs are positive and negative regulators of eukaryotic gene expression that modulate transcript abundance by specific binding to sequence motifs located prevalently in the 3’ untranslated regions (3’-UTR) of target messenger RNAs (mRNA). Interferon-alpha-2a (IFNα) induces a large set of protein-coding genes mediating anti-proliferative and antiviral responses. Here we use a global microarray-based microRNA detection platform to identify genes that are induced by IFNα in hepatoma- or melanoma-derived human tumor cell lines. Despite the enormous differences in expression levels between these models, we were able to identify microRNAs that are upregulated by IFNα in both lines, suggesting the possibility that interferon-regulated microRNAs (IRmiRs) are involved in the transcriptional repression of mRNA relevant to cytokine responses.
Project description:STAT1 plays a cental role in the induction of interferon-stimulated genes, but interferon alpha can activate a STAT1-independent pathway that leads to gene expression. We performed microarray analysis to examine whether like interferon alpha, interferon lambda, a newly discovered interferon, can induce the expression of interferon-stimulated genes in the absence of STAT1. Control and STAT1 knockout Huh-7.5 hepatoma cells were left untreated or treated with 1000 U/ml of human interferon alpha 2a or interferon lambda 1 (PBL) for 24 h, and total RNA was extracted. Sense-strand DNA was generated from 200 ng of total RNA, fragmented, and labeled using a GeneChip WT Plus Reagent Kit (Affymetrix). Six samples were obtained and each sample was anlyzed using one GeneChip.
Project description:A hallmark of resistance to type I interferons (IFNs) is the lack of antiproliferative responses. Foser et al. 2006 have shown that costimulation with IFN-alpa and transforming growth factor beta-1 (TGF-beta) potentiates antiproliferative activity in a sensitive (ME15) and resistant (D10) human melanoma cell line. Gene induction by small concentration of interferon-alpha-2a (100 U/ml) was analyzed in human cancer cell lines with differences in sensitivity to IFN-alpha and TGF-beta. Among other antiproliferative genes we found upregulated IFITM3 gene expression levels and inducibility of this antiproliferative protein in interferon sensitive cell lines.
2010-05-16 | GSE21158 | GEO
Project description:Interferon alpha treated cultured human megakaryocytes
Project description:This protocol will evaluate the activity of 5-Fluorouracil (FUra) given as a 1 hour infusion in combination with leucovorin (LV) and interferon IFN alpha-2a in patients with advanced, measurable colorectal cancer.
