RNA expression analysis after MCF-7 cell treatment with demethylating agent 5-Aza-2’-deoxycitidine (5-Aza)
Ontology highlight
ABSTRACT: Transcriptional profiling of MCF-7 cells treated with 5-Aza for 96 h. Relative abundance to untreated control cells was used to estimate the effect of DNA demethylation on the expression of the RNAs. Two-condition experiment, 5-Aza-treated vs. untretated MCF-7 cells. Biological replicates: 2. Technical replicates: 2.
Project description:Transcriptional profiling of DU-145 cells treated with 5-Aza for 72 h. Relative abundance to untreated control cells was used to estimate the effect of DNA demethylation on the expression of the RNAs. Two-condition experiment, 5-Aza-treated vs. untreated DU-145 cells. Biological replicates: 2. Technical replicates: 2.
Project description:Transcriptional profiling of Mia PaCa 2 cells treated with 5-Aza for 96 h. Relative abundance to untreated control cells was used to estimate the effect of DNA demethylation on the expression of the RNAs. Two-condition experiment, 5-Aza-treated vs. untretated Mia PaCa 2 cells. Biological replicates: 2. Technical replicates: 2.
Project description:Combination therapies targeting malignancies aim to increase treatment efficacy and reduce toxicity. Hypomethylating drug 5-Aza-2’-deoxycytidine (5-Aza-2’) enhances transcription of tumor suppressor genes and induces replication errors via entrapment of DNMT1. Post-translational modification by SUMO plays major roles in the DNA damage response and is required for degradation of entrapped DNMT1. Here, we combine SUMOylation inhibitor TAK981 and DNA-hypomethylating agent 5-Aza-2’ to improve treatment of MYC driven hematopoietic malignancies, since MYC overexpressing tumors are sensitive to SUMOylation inhibition. We studied the classical MYC driven malignancy Burkitt lymphoma, as well as diffuse large B-cell lymphoma (DLBCL) with and without MYC translocation. SUMO inhibition prolonged the entrapment of DNMT1 to DNA, resulting in DNA damage. An increase in DNA damage was observed in cells co-treated with TAK981 and 5-Aza-2’. Both drugs synergized to reduce cell proliferation in vitro in a B cell lymphoma cell panel, including Burkitt lymphoma and DLBCL. In vivo experiments combining TAK981 (25 mg/kg) and 5-Aza-2’ (2.5 mg/kg) showed a significant reduction in outgrowth of Burkitt lymphoma in an orthotopic xenograft model. In contrast, single dosing of TAK981 was ineffective and single dosing of 5-Aza-2’ only led to a modest outgrowth reduction. TAK981 and 5-Aza-2’ synergize to reduce B cell Lymphoma outgrowth in vitro and in vivo. SUMOylation is a key-player in the repair of DNA damage, hence upon TAK981 treatment the repair of DNA damage induced by 5-Aza-2’ treatment is impaired. Our results demonstrate the potential of tailored combination of drugs, based on insight in molecular mechanisms, to improve the efficacy of cancer therapies.
Project description:Transcriptional profiling of MCF-7 cells treated with 5-Aza for 96 h. Relative abundance to untreated control cells was used to estimate the effect of DNA demethylation on the expression of the RNAs.
Project description:Combination therapies targeting malignancies aim to increase treatment efficacy and reduce toxicity. Hypomethylating drug 5-Aza-2’-deoxycytidine (5-Aza-2’) enhances transcription of tumor suppressor genes and induces replication errors via entrapment of DNMT1. Post-translational modification by SUMO plays major roles in the DNA damage response and is required for degradation of entrapped DNMT1. Here, we combine SUMOylation inhibitor TAK981 and DNA-hypomethylating agent 5-Aza-2’ to improve treatment of MYC driven hematopoietic malignancies, since MYC overexpressing tumors are sensitive to SUMOylation inhibition. We studied the classical MYC driven malignancy Burkitt lymphoma, as well as diffuse large B-cell lymphoma (DLBCL) with and without MYC translocation. SUMO inhibition prolonged the entrapment of DNMT1 to DNA, resulting in DNA damage. An increase in DNA damage was observed in cells co-treated with TAK981 and 5-Aza-2’. Both drugs synergized to reduce cell proliferation in vitro in a B cell lymphoma cell panel, including Burkitt lymphoma and DLBCL. In vivo experiments combining TAK981 (25 mg/kg) and 5-Aza-2’ (2.5 mg/kg) showed a significant reduction in outgrowth of Burkitt lymphoma in an orthotopic xenograft model. In contrast, single dosing of TAK981 was ineffective and single dosing of 5-Aza-2’ only led to a modest outgrowth reduction. TAK981 and 5-Aza-2’ synergize to reduce B cell Lymphoma outgrowth in vitro and in vivo. SUMOylation is a key-player in the repair of DNA damage, hence upon TAK981 treatment the repair of DNA damage induced by 5-Aza-2’ treatment is impaired. Our results demonstrate the potential of tailored combination of drugs, based on insight in molecular mechanisms, to improve the efficacy of cancer therapies.
Project description:Transcriptional profiling of DU-145 cells treated with 5-Aza for 72 h. Relative abundance to untreated control cells was used to estimate the effect of DNA demethylation on the expression of the RNAs.
Project description:Transcriptional profiling of Mia PaCa 2 cells treated with 5-Aza for 96 h. Relative abundance to untreated control cells was used to estimate the effect of DNA demethylation on the expression of the RNAs.
Project description:Transcriptional profiling of HeLa cells treated with α-amanitin for 9 h. Relative abundance to untreated control cells was used to evaluate the biogenesis of lncRNAs by RNA polymerase II. Two-condition experiment, alpha-amanitin-treated vs. untretated HeLa cells. Biological replicates: 4 with dye-swap
Project description:HeLa cells were fractioned in nucleus and cytoplasm to investigate the subcellular distribution of lncRNAs. Two-condition experiment, nuclear fraction vs. cytoplasmatic fraction from HeLa cells. Biological replicates: 2 with dye-swap
Project description:Transcriptional profiling of HeLa cells treated with actinomycin D for increasing amounts of time. Relative abundance to control cells was used to estimate the half-life of lncRNAs. Two-condition experiment, actinomycin D-treated vs. untreatted HeLa cells. Biological replicates: 2. Technical replicates: 2.