Transcription profiling of human acute myeloid leukemia cell line OCI/AML2 with the anti-parasitic ivermectin
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Mahadeo Sukhai
PROVIDER: E-MEXP-2528 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Human acute myeloid leukemia cell lines OCI-AML2 and OCI-AML3 were used in a CRISPR/Cas9-mediated approach to specifically target DDX3X’s gene sequences encoding the RNA binding domain of the helicase. DDX3X RNA binding domain is bipartite in the two halves of the helicase core. sgRNAs were designed to target both halves of the domain (named RNA binding domain A and B – RBDA and RBDB). We performed RNA-seq to observe the gene expression changes in both OCI-AML2 and OCI-AML3 cell lines following the not-combined CRISPR/Cas9 –mediated targeting of both regions of the DDX3X RNA binding domain. Control CRISPR/Cas9 performed with no sgRNA expressing vector (named “empty vector”) was performed in both cell lines. The latter condition was used as a control for gene expression changes analysis, for each cell line.
2019-11-23 | E-MTAB-6241 | biostudies-arrayexpress
Project description:We have investigated the transcriptomic response of the model nematode Caenorhabditis elegans to ivermectin (IVM); an important anthelmintic for human and animal parasite control. The transcriptomic response of the mutant strain DA1316 avr-14(ad1302); avr-15(ad1250); glc-1(pk54), which is highly resistant to ivermectin due to null mutations in three glutamate-gated chloride channel subunits, was examined. Despite the resistant nature of this strain, pharyngeal pumping rate was decreased following 4 hrs exposure to 100ng/ml and 1?g/ml ivermectin resulting in significant change in the expression level of genes associated with a fasting response. Matched cultures of synchronised C. elegans were grown to L4 stage on standard NGM plates with an OP50 bacterial lawn. The nematodes were then transferred to NGM plates containing 100ng/ml ivermectin, 1?g/ml ivermectin, or DMSO excipient only (control) for 4 hours. RNA was extracted from five biological replicates including controls for both the 100ng/ml ivermectin and 1?g/ml ivermectin experiments and hybridised to Affymetrix arrays.
2011-04-01 | E-GEOD-22660 | biostudies-arrayexpress
Project description:We have investigated the transcriptomic response of the model nematode Caenorhabditis elegans to ivermectin (IVM); an important anthelmintic for human and animal parasite control. The transcriptomic response of the mutant strain DA1316 avr-14(ad1302); avr-15(ad1250); glc-1(pk54), which is highly resistant to ivermectin due to null mutations in three glutamate-gated chloride channel subunits, was examined. Despite the resistant nature of this strain, pharyngeal pumping rate was decreased following 4 hrs exposure to 100ng/ml and 1μg/ml ivermectin resulting in significant change in the expression level of genes associated with a fasting response.
2011-04-01 | GSE22660 | GEO
Project description:Here, we show that ivermectin suppress prostate cancer progression by inhibiting AR signaling pathway and attenuate cellular DNA damage repair capacity. We applied an integrated omics profiling including RNA-seq and Thermal proteome, that found pioneer factor Forkhead Box Protein A1 (FOXA1) and Non-homologous End Joining (NHEJ) repair executer Ku70/Ku80 was the direct target of Ivermectin in prostate cancer. Ivermectin binds to these two proteins and block their biological function, which results in blockade of AR signaling transcription and deficiency of DNA double-strand breaks (DSBs) repair system, and thereby leads to G0/G1 arrest and trigger synthetic lethality Our findings demonstrate both the effect and target of Ivermectin in prostate cancer comprehensively and systemically, indicating that use of Ivermectin may constitute a new therapeutic approach for prostate cancer.
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Project description:In this study, we analyzed transcriptomic profiles from ivermectin-treated and -untreated B. malayi adult females using Next Generation RNA Sequencing technology at different concentrations (100 nM, 300 nM and 1 µM) and time points (24, 48, 72 h, and 5 days). Our analysis revealed altered expression of multiple genes involved in meiosis, as well as oxidative phosphorylation which were significantly down-regulated as early as 24 hours post-exposure. RNA interference phenotypes of the orthologs of these down-regulated genes in C. elegans include âmaternal sterileâ, âembryonic lethalâ, âlarval arrestâ, âlarval lethalâ, âreduced brood sizeâ and âegg shape variableâ. These changes reflect and provide insight into the mechanisms involved in ivermectin-induced reduction in microfilaria output and impaired fertility, embryogenesis, and larval development. Transcriptomic changes over several different time points and concentrations.
2016-07-27 | E-GEOD-75339 | biostudies-arrayexpress
Project description:In this study, we analyzed transcriptomic profiles from ivermectin-treated and -untreated B. malayi adult females using Next Generation RNA Sequencing technology at different concentrations (100 nM, 300 nM and 1 µM) and time points (24, 48, 72 h, and 5 days). Our analysis revealed altered expression of multiple genes involved in meiosis, as well as oxidative phosphorylation which were significantly down-regulated as early as 24 hours post-exposure. RNA interference phenotypes of the orthologs of these down-regulated genes in C. elegans include âmaternal sterileâ, âembryonic lethalâ, âlarval arrestâ, âlarval lethalâ, âreduced brood sizeâ and âegg shape variableâ. These changes reflect and provide insight into the mechanisms involved in ivermectin-induced reduction in microfilaria output and impaired fertility, embryogenesis, and larval development. Transcriptomic changes over several different time points and concentrations.
2016-07-27 | E-GEOD-75340 | biostudies-arrayexpress
Project description:RNA pools were labeled and hybridized to an Affymetrix HG-U133 Plus 2.0 array (Affymetrix, USA). Results derived from untreated OCI-AML cells (sample) were compared to results from OCI-AML treated with TAT-2 (1 mg/mL) for 3 h by M-^Scomparative analysisM-^T with GCOS software. Data were then analyzed using GenePicker software, using a fold change cutoff >1.5 and a p-value of 0.05.
2011-02-07 | E-MEXP-3088 | biostudies-arrayexpress
Project description:Endogenous bioelectric signaling via changes in cellular resting potential (Vmem) is a key regulator of patterning during regeneration and embryogenesis in numerous model systems. Depolarization of Vmem has been functionally implicated in de-differentiation, tumorigenesis, anatomical re-specification, and appendage regeneration. However, no unbiased analyses have been performed to understand genome-wide transcriptional responses to Vmem change in vivo. Moreover, it is unknown which genes or gene networks represent conserved targets of bioelectrical signaling across different patterning contexts and species. Here, we use microarray analysis to comparatively analyze transcriptional responses to specific Vmem depolarization. We compare the response of the transcriptome during embryogenesis (Xenopus development), regeneration (Axolotl regeneration), and stem cell differentiation (human mesenchymal stem cells in culture) to identify common networks across model species that are associated with depolarization. Both sub-network enrichment and PANTHER analyses identified a number of key genetic modules as targets of Vmem change, and also revealed important (well-conserved) commonalities in bioelectric signal transduction, despite highly diverse experimental contexts and species. Depolarization regulates specific transcriptional networks across all three germ layers (ectoderm, mesoderm and endoderm) such as cell differentiation and apoptosis, and this information will be used for developing mechanistic models of bioelectric regulation of patterning. Moreover, our analysis reveals that Vmem change regulates transcripts related to important disease pathways such as cancer and neurodegeneration, which may represent novel targets for emerging electroceutical therapies. All axolotls used in these experiments were bred in the axolotl facility at the University of Minnesota under the IACUC protocol #1201A08381. Axolotls of 2â3 cm were used for all in vivo experiments, and animals were kept in separate containers and fed daily with artemia; water was changed daily. Animals were anesthetized in 0.01% p-amino benzocaine (Sigma) before microinjection was performed. There were 9 microarrays conducted, and these were ivermectin-treated (n=3). Experimental Design: Ivermectin injection Ivermectin or vehicle only (water) was pressure injected into the central canal of the spinal cord, and this was visualized by the addition of Fast Green into the solution. Directly after injection, a portion of the spinal cord was surgically removed and the animals were placed back into water in individual containers. One day post injury (1dpi) animals were anesthetized again and the area of the injury was removed. Tissue from 10 animals were pooled for each microarray replicate. Mature - Uninjured spinal cord tissue Sc Crush- spinal cord tissue 1 day after injury Ivermectin - Ivermectin injected spinal cord tissue 1 day after injury.
2016-07-03 | E-GEOD-72096 | biostudies-arrayexpress
Project description:Rhipicephalus microplus is among the critical tick parasite of cattle farming globally. However, the massive use of ivermectin last decades induced the generation of the tick-resistant population. Unfortunately, despite extensive research the mode of action of ivermectin remains unclear. Due to the limited molecular information related to the resistance of R. microplus to ivermectin, we carried out a midgut comparative proteomics study between susceptible and resistant tick. Our tissues specificity approach also included tandem mass tags (TMT) couple to synchronous precursor selection (SPS)-MS3. Our proteomics scrutiny exhibits key biological process associated with blood digestion and anticoagulation in midgut. In addition, we could observe the significant shutdown of the translation mechanism in susceptible thinks. At the same time, resistant thick exhibited the over-accumulation of cytochrome P450, glutathione-S-transferase, and ABC transporters. A similar trend was observed in proteins like glutathione peroxides glutaredoxin, sulfiredoxin, and disulfide-isomerase, which suggest a possible activation of the oxidative metabolism as a potential strategy to cope with ivermectin treatment.
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Project description:Salamanders, such as the Mexican axolotl, are some of the few vertebrates fortunate in their ability to regenerate diverse structures after injury. Unlike mammals they are able to regenerate a fully functional spinal cord after injury. However, the early signals required to initiate a pro-regenerative response after spinal cord injury is not well understood. To address this question we developed a spinal cord injury model in axolotls and used in vivo imaging of ion sensitive dyes and determined that spinal cord injury induces a rapid and dynamic change in the resting membrane potential of ependymoglial cells. Prolonged depolarization of ependymoglial cells after injury inhibits glial cell proliferation and subsequent axon regeneration. Using transcriptional profiling we identified c-Fos as a key voltage sensitive early response gene that is expressed specifically in the ependymoglial cells after injury. This data establishes that dynamic changes in the membrane potential after injury are essential for regulating the specific spatiotemporal expression of c-Fos that is critical for promoting faithful spinal cord regeneration in axolotl. All axolotls used in these experiments were bred in the axolotl facility at the University of Minnesota under the IACUC protocol #1201A08381. Axolotls of 2â3 cm were used for all in vivo experiments, and animals were kept in separate containers and fed daily with artemia; water was changed daily. Animals were anesthetized in 0.01% p-amino benzocaine (Sigma) before microinjection was performed. Experimental Design: Ivermectin injection Ivermectin or vehicle only (water) was pressure injected into the central canal of the spinal cord, and this was visualized by the addition of Fast Green into the solution. Directly after injection, a portion of the spinal cord was surgically removed and the animals were placed back into water in individual containers. One day post injury (1dpi) animals were anesthetized again and the area of the injury was removed. Tissue from 10 animals were pooled for each microarray replicate.
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