Drosophila CNS mitochondrial dysfunction with Ras/MAPK inhibition microarray
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA463815 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Mitochondrial dysfunction causes biophysical, metabolic and signalling changes that alter homeostasis and reprogram cells. We used a Drosophila model in which TFAM is overexpressed in the nervous system with or without Ras/MAPK pathway inhibition, by knock-down of the ETS transcription factor pointed, to investigate the how mitochondrial dysfunction and Ras/MAPK signalling affect the transcriptome. We used microarray analysis to investigate gene expression in cases of mitochondrial dysfunction in the CNS with or without Ras/MAPK pathway inhibition by knock-down of pointed (Pnt) and anterior open (Aop).
2018-05-05 | GSE114054 | GEO
Project description:Mitochondrial DNA (mtDNA) encodes essential components of the respiratory chain and loss of mtDNA leads to mitochondrial dysfunction and neurodegeneration. Mitochondrial transcription factor A (TFAM) is an essential component of mtDNA replication and a regulator of mitochondrial copy number in cells. Studies have shown that TFAM knockdown leads to mitochondrial dysfunction and respiratory chain deficiencies. Using gene expression analysis, we aimed to investigate the effects of mtDNA dysfunction in the CNS at the molecular level. We used microarray analysis to investigate gene expression in cases of mitochondrial dysfunction in the CNS. RNA was purified from the late third instar larval CNS from control larvae, or larvae over-expressing mitochondrial transcription factor A (TFAM) in post-mitotic neurons using the neuron specific driver nsyb-Gal4. Three replicates are included for each condition.
2013-12-20 | E-GEOD-53509 | biostudies-arrayexpress
Project description:Mitochondrial DNA (mtDNA) encodes essential components of the respiratory chain and loss of mtDNA leads to mitochondrial dysfunction and neurodegeneration. Mitochondrial transcription factor A (TFAM) is an essential component of mtDNA replication and a regulator of mitochondrial copy number in cells. Studies have shown that TFAM knockdown leads to mitochondrial dysfunction and respiratory chain deficiencies. ATP synthase is Complex V of the mitochondrial respiratory chain. It is driven by a proton gradient between the intermembrane space and the mitochondrial matrix and generates the majority of cellular ATP. The knockdown of coupling factor 6 (Cf6), one of the components of the proton channel F0, causes dysfunction in the complex, leading to mitochondrial dysfunction and respiratory chain deficiencies. Using gene expression analysis, we aimed to investigate the effects of mtDNA dysfunction in the CNS at the molecular level.
2013-12-20 | GSE53509 | GEO
Project description:We performed tanscriptional profiling of ARPE19 and four isogenic transformed cells lines in which Ras or two downstream pathways, MAPK or PI3K/mTOR, were up-regulated. The purpose of this study is to understand how Ras signaling impacts kinetochore function.
2022-09-21 | GSE172512 | GEO
Project description:Drosophila CNS mitochondrial dysfunction with ATF4 inhibition RNA-Seq
| PRJNA526877 | ENA
Project description:Basal cell carcinomas (BCCs) rely on Hedgehog (HH) pathway growth signal amplification by the microtubule-based organelle, the primary cilium. Despite naïve tumors responsiveness to Smoothened inhibitors (Smoi), resistance in advanced tumors remains frequent. While the resistant BCCs usually maintain HH pathway activation, squamous cell carcinomas with Ras/MAPK pathway activation also arise, with the molecular basis of tumor type and pathway selection still obscure. Here we identify the primary cilium as a critical determinant controlling tumor pathway switching. Strikingly, Smoi-resistant BCCs possess an increased mutational load in ciliome genes, resulting in reduced primary cilia and HH pathway activation compared to naive or Gorlin patient BCCs. Gene set enrichment analysis of resistant BCCs with a low HH pathway signature reveals increased Ras/MAPK pathway activation. Tissue analysis confirms an inverse relationship between primary cilia presence and Ras/MAPK activation, and primary cilia removal in BCCs potentiates Ras/MAPK pathway activation. Moreover, activating Ras in HH-responsive cell lines confers resistance to both canonical (vismodegib) and non-canonical (aPKC and MRTF inhibitors) HH pathway inhibitors, while conferring sensitivity to MAPK inhibitors. Our results provide new insights into BCC treatment and identify the primary cilium as an important lineage gatekeeper, preventing HH to Ras/MAPK pathway switching.
2018-10-10 | GSE120954 | GEO
Project description:Approximately 50% of prostate cancers have chromosomal translocations resulting in the over-expression one of four ETS family transcription factors. However, it is not known why these four four family members are selected for oncogenic roles, while other ETS proteins are not. We found that the four oncogenic ETS family members have a specific role in prostate cell migration. Using chromatin immunoprecipitation coupled with next-generation sequencing, this specific biological function was matched to a specific set of genomic targets highlighted by the presence of an AP-1 binding site. ETS/AP-1 binding sites are prototypical Ras-responsive elements, but oncogenic ETS proteins could activate a Ras/MAPK transcriptional program in the absence of MAPK activation. These findings indicate that the specific function of ETS proteins over-expressed in prostate cancer is the activation of a Ras/MAPK gene expression program in the absence of signaling pathway mutations. 16 samples were analyzed, comprised of four replicates each of four different biological conditions. RNA from U0126 treated RWPE-1 empty vector cell RNA serves as a control for each experiment. Cell lines have retroviral expression constructs expressing either empty vector, Flag-ERG, or Flag-ETV1.
2011-10-18 | E-GEOD-29438 | biostudies-arrayexpress
Project description:Hyperactive RAS/MAPK introduces cancer-specific mitotic vulnerabilities
| PRJNA723590 | ENA
Project description:Approximately 50% of prostate cancers have chromosomal translocations resulting in the over-expression one of four ETS family transcription factors. However, it is not known why these four four family members are selected for oncogenic roles, while other ETS proteins are not. We found that the four oncogenic ETS family members have a specific role in prostate cell migration. Using chromatin immunoprecipitation coupled with next-generation sequencing, this specific biological function was matched to a specific set of genomic targets highlighted by the presence of an AP-1 binding site. ETS/AP-1 binding sites are prototypical Ras-responsive elements, but oncogenic ETS proteins could activate a Ras/MAPK transcriptional program in the absence of MAPK activation. These findings indicate that the specific function of ETS proteins over-expressed in prostate cancer is the activation of a Ras/MAPK gene expression program in the absence of signaling pathway mutations. ChIP sequencing two transcription factors in PC3 cells, four transcription factors plus a FLAG control in RWPE-1 cells and input DNA sequencing from each cell line.
2011-10-19 | E-GEOD-29808 | biostudies-arrayexpress
Project description:Approximately 50% of prostate cancers have chromosomal translocations resulting in the over-expression one of four ETS family transcription factors. However, it is not known why these four four family members are selected for oncogenic roles, while other ETS proteins are not. We found that the four oncogenic ETS family members have a specific role in prostate cell migration. Using chromatin immunoprecipitation coupled with next-generation sequencing, this specific biological function was matched to a specific set of genomic targets highlighted by the presence of an AP-1 binding site. ETS/AP-1 binding sites are prototypical Ras-responsive elements, but oncogenic ETS proteins could activate a Ras/MAPK transcriptional program in the absence of MAPK activation. These findings indicate that the specific function of ETS proteins over-expressed in prostate cancer is the activation of a Ras/MAPK gene expression program in the absence of signaling pathway mutations.
2011-10-19 | GSE29438 | GEO