Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-5823
PROVIDER: PRJNA97209 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We sought to determine the effects of SMARCA4 and SMARCA2 depletion in prostate cancer cell lines. We performed siRNA-mediated knock-down of SMARCA4 and SMARCA2 in an androgen-sensitive (LNCaP) cell line and in a castration-resistant prostate cancer (CRPC)-adenocarcinoma cell line (22Rv1) and compared global transcriptional alterations using RNA-seq.
| EGAS00001004177 | EGA
Project description:De novo lipogenesis is activated in most cancers. Several lipogenic enzymes are implicated in oncogenesis and represent potential cancer therapeutic targets. RNA interference-mediated depletion of ATP citrate lyase (ACLY), the enzyme that catalyzes the first step of de novo lipogenesis, leads to growth suppression in a subset of human cancer cells. Here we demonstrate the molecular basis and potential biomarkers for ACLY-targeting therapy. First, suppression of cancer cell growth by ACLY depletion involves down-regulation of fatty acid elongase ELOVL6 at the transcriptional level. Lipid profiling revealed that ACLY depletion alters fatty acid composition in triglyceride; increased palmitate and decreased longer fatty acids, in accordance with ELOVL6 down-regulation. Second, ACLY depletion increases reactive oxygen species (ROS), whereas addition of antioxidant reduces ROS and attenuates the growth suppression. Third, ACLY depletion or ROS stimulation induce phosphorylation of AMP-activated protein kinase (AMPK), a sensor of energy and lipid metabolism. Analysis of various cancer cell lines revealed that the levels of AMPK phosphorylation (p-AMPK) correlate with the basal ROS levels, and that cancer cells with low basal p-AMPK (i.e., low basal ROS) levels are highly susceptible to ACLY depletion-mediated growth suppression. Finally, in clinical colon cancer tissues, p-AMPK levels are significantly decreased in aggressive tumors and correlate with the levels of 8-hydroxydeoxyguanosine, a hallmark of ROS stimulation. Together, these data suggest that ACLY inhibition suppresses cancer growth via palmitate-mediated lipotoxicity, and p-AMPK could be a predictive biomarker for its therapeutic outcome. Two cell lines are treated with ACLY siRNA. The samples include controls of each cell line.
2014-04-13 | E-GEOD-37243 | biostudies-arrayexpress
Project description:The MYC axis is commonly disrupted in cancer, mostly by activation of the MYC family of oncogenes, but also by genetic inactivation of MAX, the obligate partner of MYC, and of the MAX partner, MGA, both of which are members of the polycomb repressive complex, ncPRC1.6. While the oncogenic properties of the MYC family have been extensively studied, the tumor suppressor functions of MAX and MGA and the role of the MYC genes in MAX-mutant cells remain unclear. To address these knowledge gaps, we used chromatin immunoprecipitation, RNA-sequencing and mass spectrometry-based proteomic analysis in MAX-restituted and MYC oncogenic-transformed cell lines derived from human small cell lung cancer (SCLC), which is a high-grade neuroendocrine type of lung cancer. We found that MAX-mutant SCLC cells express ASCL1 and ASCL1-dependent targets, implying that these cells belong to the ASCL1-dependent group of SCLCs. In the absence of MAX, even after ectopic overexpression of MYC, we found no recruitment of MYC to the DNA. Furthermore, MAX reconstitution triggered pro-differentiation expression profiles that shifted when MAX and oncogenic MYC were co-expressed. Although ncPRC1.6 could be formed, the lack of MAX restricted global MGA occupancy, selectively driving its recruitment towards E2F6 motifs. Conversely, MAX restitution enhanced MGA occupancy and global gene repression of genes involved in different functions, including stem-cell and DNA repair/replication. Our data reveal that MAX-mutant SCLCs have ASCL1 characteristics, and are MYC-independent, and that their oncogenic features include deficient ncPRC1.6-mediated gene repression.
2021-09-22 | PXD017658 | Pride
Project description:RBM39 is a crucial component of the spliceosome that is critical for the integrity of mature mRNA, while depletion of RBM39 by Indisulam significantly increases RNA splicing defects. The antitumor activity of Indisulam is partially attributed to its inhibitory effects on cell cycle progression. To identify the key effector proteins responsible for cell cycle arrest following RBM39 depletion, we employed a multi-omics approach utilizing two chemotypes of RBM39 degraders: Indisulam and CB039. Through proteomics analysis, RNA sequencing, and DepMap cancer cell line dependency analysis, we identified CEP192 as a key gene that exhibited dependency in 96% of 1,100 cancer cell lines. In a panel of eight cancer cell lines, we observed consistent phenotypes upon treatment with CB039 and Indisulam, including skipping of CEP192 exon 42 and downregulation of the CEP192 protein. Mechanistically, treatment with CB039 and Indisulam, as well as CEP192 knockdown via RNA interference, resulted in arrest of cell cycle progression at the G2/M phase. This treatment also induced a disorganized spindle phenotype, as well as condensed and undivided chromosomes. In summary, this work enhances our understanding of the anti-mitotic mechanism underlying RBM39 molecular glue degraders.
2025-03-20 | PXD056341 | Pride
Project description:Multiple myeloma (MM) is a malignant plasma cell disorder and frequently characterized by the 16 dysregulation of the MYC oncogene, which is associated with poor prognosis and disease progression. While MYC's involvement in transcriptional regulation is well-established, the functional role of MYC target proteins and the impact on post-transcriptional processes in MM cells remain poorly understood. This study employed Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC) coupled with mass spectrometry analysis to investigate the effects of MYC depletion on the proteome of MM cells. The results revealed that MYC primarily regulates translational processes. Specifically, the three RNA-binding proteins (RBPs) 4EBP1, hnRNPC, and LARP1, were prominently down-regulated upon MYC depletion in MM cells. Notably, high expression levels of these proteins were correlated with poor survival and disease progression in MM patients. These findings highlight the critical role of MYC in the regulation of translation and identify 4EBP1, hnRNPC, and LARP1 as MYC target proteins. Targeting these proteins may offer new therapeutic strategies and prognostic markers for MM, potentially improving patient outcomes. This study provides valuable insights into the post-transcriptional regulatory mechanisms mediated by MYC and opens avenues for further research in understanding and treating this devastating disease.
2023-06-15 | MSV000092169 | MassIVE
Project description:MPV17 is described as a mitochondrial inner membrane channel. Although its function remains elusive, mutations in the MPV17 gene results in hepato-cerebral mitochondrial DNA depletion syndrome. However, in this study, we show that MPV17 silencing does not induce depletion in mitochondrial DNA content in cancer cells. We also show that MPV17 silencing does not control cancer cell proliferation, despite the fact that we initially observed a reduced proliferation rate in five MPV17-silenced cancer cell lines with two different shRNAs. This reduced proliferation phenotype might be due to off-target effects of shRNA-mediated knockdown. RNA interference has been a quantum leap in the field of functional genomic. This scientific breakthrough is a straightforward approach to monitor the aftermaths of the functional loss of a specific gene. However, one must beware the illusion of control that comes with any new technology and acknowledge the unintended events embedded to it. Our results illustrate the insidiousness of off-target effects and emphasize the caution that is required when scientific conclusions are drawn from a work based on lentiviral vector-based gene silencing. They also clearly demonstrate the need to systematically perform a rescue experiment in order to ascertain the specific nature of the experimental results.
2019-08-01 | E-MTAB-8108 | biostudies-arrayexpress
Project description:Interferons have been ascribed to mediate antitumor effects. IRF-1 is a major target gene of interferons. It inhibits cell proliferation and oncogenic transformation. Here we show that 60% of all mRNAs deregulated by oncogenic transformation mediated by c-myc and H-ras are reverted to the expression levels of non-transformed cells by IRF-1. These include cell cycle regulating genes. Activation of IRF-1 decreases cyclin D1 expression and CDK4 kinase activity concomitant with dephosphorylation of pRb. These effects of IRF-1 are mediated by inhibition of the MEK-ERK pathway and a transcriptional repression of cyclin D1. IRF-1 mediated effects on cell cycle progression were found to be overridden by ectopic expression of cyclin D1. Ablation of cyclin D1 by RNA interference experiments prevents transformation and tumor growth in nude mice. The data demonstrate that cyclin D1 is a key target for IRF-1 mediated tumor suppressive effects. Experiment Overall Design: 3 samples were analysed, two replicates per sample. NIH3T3 cells were compared with myc/ras transformed NIH3T3 cells and with IRF1 expressing myc/ras transformed cells.
2008-06-14 | E-GEOD-6505 | biostudies-arrayexpress
Project description:DHX15 has been implicated in RNA splicing and ribosome biogenesis, primarily functioning as an RNA helicase. To systematically assess the cellular role of DHX15, we conducted proteomic analysis to investigate the landscape of DHX15 interactome, and identified MYC as a binding partner. DHX15 co-localizes with MYC in cells and directly interacts with MYC in vitro. Importantly, DHX15 contributes to MYC protein stability at the post-translational level and independent of its RNA binding capacity. Mechanistic investigation reveals that DHX15 interferes the interaction between MYC and FBXW7, thereby preventing MYC polyubiquitylation and proteasomal degradation. Consequently, abrogation of DHX15 drastically inhibits MYC-mediated transcriptional output. While DHX15 depletion blocks T-cell development and leukemia cell survival as we recently reported, overexpression of MYC significantly rescues the phenotypic defects. These findings shed new light on the essential role of DHX15 in mammalian cells and suggest that maintaining sufficient MYC expression is a significant contributor to DHX15-mediated cellular functions.
2024-01-26 | PXD046692 | Pride
Project description:Microarray experiments were carried out to ascertain whether TOP2β is required for DHT induced androgen receptor target gene expression. We investigated the effect of pharmacological inhibition or RNA interference-mediated depletion of TOP2β on gene expression in androgen-dependent LNCaP prostate cancer cells.
2010-07-04 | GSE19445 | GEO
Project description:De novo lipogenesis is activated in most cancers. Several lipogenic enzymes are implicated in oncogenesis and represent potential cancer therapeutic targets. RNA interference-mediated depletion of ATP citrate lyase (ACLY), the enzyme that catalyzes the first step of de novo lipogenesis, leads to growth suppression in a subset of human cancer cells. Here we demonstrate the molecular basis and potential biomarkers for ACLY-targeting therapy. First, suppression of cancer cell growth by ACLY depletion involves down-regulation of fatty acid elongase ELOVL6 at the transcriptional level. Lipid profiling revealed that ACLY depletion alters fatty acid composition in triglyceride; increased palmitate and decreased longer fatty acids, in accordance with ELOVL6 down-regulation. Second, ACLY depletion increases reactive oxygen species (ROS), whereas addition of antioxidant reduces ROS and attenuates the growth suppression. Third, ACLY depletion or ROS stimulation induce phosphorylation of AMP-activated protein kinase (AMPK), a sensor of energy and lipid metabolism. Analysis of various cancer cell lines revealed that the levels of AMPK phosphorylation (p-AMPK) correlate with the basal ROS levels, and that cancer cells with low basal p-AMPK (i.e., low basal ROS) levels are highly susceptible to ACLY depletion-mediated growth suppression. Finally, in clinical colon cancer tissues, p-AMPK levels are significantly decreased in aggressive tumors and correlate with the levels of 8-hydroxydeoxyguanosine, a hallmark of ROS stimulation. Together, these data suggest that ACLY inhibition suppresses cancer growth via palmitate-mediated lipotoxicity, and p-AMPK could be a predictive biomarker for its therapeutic outcome.
2014-04-13 | GSE37243 | GEO