Transcriptomic alterations in stably overexpressing (OE) clones of solute carriers SLC22A10 and SLC22A15 in PANC-1 (human pancreatic cancer cell line)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE155909 | GEO | 2021/05/31
REPOSITORIES: GEO
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Project description:The goal of this study was to identify preadipocyte signature genes that are dependent in aldehyde dehydrogenase 1a1 (Aldh1a1) by comparison genomes of the immortalized wild type and Aldh1a1-/- preadipocytes. Gene expression was measured using theAffymetrix GeneChip Mouse Gene ST 2.0 arrays.
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Project description:Ovarian cancer (OC) is the leading cause of death from gynecologic malignancies in the US. Ovarian cancer stem cells (OCSCs) have been shown to drive chemoresistance and tumor progression but the mechanism remains incompletely understood. Aldehyde Dehydrogenase 1A1 (ALDH1A1) is a robust marker for cancer stem cells in ovarian and other cancers. We demonstrate that ALDH1A1 inhibition suppresses stemness, chemoresistance and senescence in ovarian cancer.
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Project description:The goal of this study was to identify preadipocyte signature genes that are dependent in aldehyde dehydrogenase 1a1 (Aldh1a1) by comparison genomes of the immortalized wild type and Aldh1a1-/- preadipocytes. Gene expression was measured using theAffymetrix GeneChip Mouse Gene ST 2.0 arrays. Murine wild type (n=3, control) and Aldh1a1-/- preadipocytes (n=3) were cultured in standard DMEM medium containing 10% of calf serum. mRNA was isolated by RNeasy (Qiagen, Valencia, CA). RNA integrity was interrogated using the Agilent 2100 Bioanalyzer (Agilent Technologies). A 100ng aliquot of total RNA was linearly amplified. Then, 5.5ug of cDNA was labeled and fragmented using the GeneChip WT PLUS reagent kit (Affymetrix, Santa Clara, CA) following the manufacturer's instructions. Labeled cDNA targets were hybridized to Affymetrix GeneChip Mouse Gene ST 2.0 arrays for 16 h at 45 °C rotating at 60rpm. The arrays were washed and stained using the Fluidics Station 450 and scanned using the GeneChip Scanner 3000. Signal intensities were quantified by Affymetrix Expression Console version 1.3.1. Background correction and quantile normalization was performed to adjust technical bias, and probe-set expression levels were calculated by RMA method. After filtering above noise cutoff, there are 9,528 probe-sets that were tested by linear model. A variance smoothing method with fully moderated t-statistic was employed for this study and was adjusted by controlling the mean number of false positives. With a combined cutoff of 2-fold change and p-value of 0.0001 (controlling 1 false positive over all probe-sets), we declared 500 probe-sets as differential gene expression between Aldh1a1-/- and WT preadipocytes.
2016-07-03 | E-GEOD-69573 | biostudies-arrayexpress
Project description:An integrated systems approach was used with bioinformatics tools to understand the the role of aldehyde dehydrogenase 1A1 (ALDH1A1) in human colon cancer cells. We combined transcriptomics, proteomics and untargeted metabolomics to gain insight into the mechanisms affected by the suppression of the ALDH1A1 gene in COLO320 cells. RNA-seq and proteomics analyses revealed 1747 transcripts and 336 proteins that were differentially expressed in cells in which the ALDH1A1 had been suppressed by shRNA transfection. Transcriptomics pathway analysis showed significant signaling pathways, such as Wnt/β-catenin (p=3.47E-6), molecular mechanisms of cancer (7.41E-5) and others relevant to lipid metabolism, such as cholesterol biosynthesis I, II and III (p=1.82E-4). Proteomics pathway analysis identified oxidative phosphorylation to be the most highly significant pathway (p=5.01E-31). Pathway analysis of the genes common to the transcriptomics and proteomics analyses revealed the asparagine biosynthesis (p=3.16E-3) and cholesterol biosynthesis the most statistically significant (p=3.36E-3). Univariate analysis of the untargeted metabolomics dataset revealed 859 ions statistically significant. Network analysis showed alterations in pathways linked to energy and lipid metabolism, such carnitine shuttle (p=5.3E-4) and fatty acid oxidation (p=2.9E-2). A systems biology approach was used to integrate all three datasets and a total of 61 pathways were generated. A direct association between the suppression of ALDH1A1 and the Vitamin A (retinol) metabolism pathway and down-regulation of retinol and the UGT2B17, UGT2A3 and PRDX6 genes was shown. In conclusion, the present results confirm the role of ALDH1A1 in retinol metabolism and shows for the first time the influence of this gene on lipid metabolism pathways that may be crucial for cholesterol synthesis in human colon cancer cells. In addition, they demonstrate how an integrated systems approach using unbiased bioinformatics tools can be used to understand the interplay of cellular pathways.
2021-09-08 | PXD012230 | Pride
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. An integrated systems approach was used with bioinformatics tools to understand the the role of aldehyde dehydrogenase 1A1 (ALDH1A1) in human colon cancer cells. We combined transcriptomics, proteomics and untargeted metabolomics to gain insight into the mechanisms affected by the suppression of the ALDH1A1 gene in COLO320 cells Methods: COLO 320 cells. Cellular ALDH1A1 expression was suppressed using MISSION shRNA lentiviral transduction particles containing validated ALDH1A1 shRNA in a pLKO plasmid vector. Scramble control shRNA in pLKO plasmid vector was used to generate control cells. Signal intensities were converted to individual base calls during a run using the system's Real Time Analysis (RTA) software. Primary analysis sample de-multiplexing and alignment to the human genome was performed using Illumina's CASAVA 1.8.2 software suite. The reads were trimmed for quality and aligned with the hg19 reference genome using TopHat2. The transcripts were assembled using Cufflinks. The assembled transcripts were used to estimate transcript abundance and differential gene expression using Cuffdiff. The results were visualized using R (CRAN) and CummeRbund Results: We combined transcriptomics, proteomics and untargeted metabolomics to gain insight into the mechanisms affected by the suppression of the ALDH1A1 gene in COLO320 cells. RNA-seq and proteomics analyses revealed 1747 transcripts and 336 proteins that were differentially expressed in cells in which the ALDH1A1 had been suppressed by shRNA transfection. Transcriptomics pathway analysis showed significant signaling pathways, such as Wnt/β-catenin (p=3.47E-6), molecular mechanisms of cancer (7.41E-5) and others relevant to lipid metabolism, such as cholesterol biosynthesis I, II and III (p=1.82E-4). Proteomics pathway analysis identified oxidative phosphorylation to be the most highly significant pathway (p=5.01E-31). Pathway analysis of the genes common to the transcriptomics and proteomics analyses revealed the asparagine biosynthesis (p=3.16E-3) and cholesterol biosynthesis the most statistically significant (p=3.36E-3). Univariate analysis of the untargeted metabolomics dataset revealed 859 ions statistically significant. Network analysis showed alterations in pathways linked to energy and lipid metabolism, such carnitine shuttle (p=5.3E-4) and fatty acid oxidation (p=2.9E-2). A systems biology approach was used to integrate all three datasets and a total of 61 pathways were generated. A direct association between the suppression of ALDH1A1 and the Vitamin A (retinol) metabolism pathway and downregulation of retinol and the UGT2B17, UGT2A3 and PRDX6 genes was shown Conclusions: the present results confirm the role of ALDH1A1 in retinol metabolism and shows for the first time the influence of this gene on lipid metabolism pathways that may be crucial for cholesterol synthesis in human colon cancer cells. In addition, they demonstrate how an integrated systems approach using unbiased bioinformatics tools can be used to understand the interplay of cellular pathways.
2019-10-08 | GSE121043 | GEO
Project description:Transcriptomic alterations in stably overexpressing (OE) clones of solute carriers SLC22A10 and SLC22A15 in PANC-1 (human pancreatic cancer cell line)
| PRJNA656196 | ENA
Project description:Sporadic colorectal cancer (CRC) insurgence and progression depend on the activation of Wnt/?-catenin signaling. Dickkopf (DKK)-1 is an extracellular inhibitor of Wnt/?-catenin signaling that also has undefined ?-catenin-independent actions. Here we report for the first time that a proportion of DKK-1 locates within the nucleus of healthy small intestine and colon mucosa, and of CRC cells at specific chromatin sites of active transcription. Moreover, we show that DKK-1 regulates several cancer-related genes including the cancer stem cell marker aldehyde dehydrogenase 1A1 (ALDH1A1) and Ral-binding protein 1-associated Eps domain-containing 2 (REPS2), which are involved in detoxification of chemotherapeutic agents. Nuclear DKK-1 expression is lost along CRC progression; however, it remains high in a subset (15%) of CRC patients (n = 699) and associates with decreased progression-free survival (PFS) after chemotherapy administration and overall survival (OS) [adjusted HR, 1.65; 95% confidence interval (CI), 1.23-2.21; P = 0.002)]. Overexpression of ALDH1A1 and REPS2 associates with nuclear DKK-1 expression in tumors and correlates with decreased OS (P = 0.001 and 0.014) and PFS. In summary, our findings demonstrate a novel location of DKK-1 within the cell nucleus and support a role of nuclear DKK-1 as a predictive biomarker of chemoresistance in colorectal cancer. Analysis of DKK-1 location and associated roles in human colon cancer cells and crypts of small and large bowel.
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Project description:Progesterone (P4) acting through its cognate receptor, the progesterone receptor (PR), plays an important role in uterine physiology. The PR knockout (PRKO) mouse has demonstrated the importance of the P4-PR axis in the regulation of uterine function. To define the molecular pathways regulated by P4-PR in the mouse uterus, Affymetrix MG U74Av2 oligonucleotide arrays were used to identify alterations in gene expression after acute and chronic P4 treatments. In the analysis, retinoic acid metabolic genes, cytochrome P 450 26a1 (Cyp26a1), alcohol dehydrogenase 5, and aldehyde dehydrogenase 1a1 (Aldh1a1); kallikrein genes, Klk5 and Klk6; and specific transcription factors, GATA-2 and Cited2 [cAMP-corticosterone-binding protein/p300-interacting transactivator with glutamic acid (E) and aspartic acid (D)-rich tail], were validated as regulated by the P4-PR axis. Identification and analysis of these responsive genes will help define the role of PR in regulating uterine biology. Ovariectomized wild-type and progesterone receptor knockout mice were injected with either vehicle or 1 mg/mouse progesterone. The injections were repeated every 12 h, and groups of mice were killed 4 h after the first injection (acute P4 treatment) or 4 h after the fourth injection (chronic P4 treatment).
2012-08-06 | E-GEOD-39920 | biostudies-arrayexpress
Project description:Progesterone (P4) acting through its cognate receptor, the progesterone receptor (PR), plays an important role in uterine physiology. The PR knockout (PRKO) mouse has demonstrated the importance of the P4-PR axis in the regulation of uterine function. To define the molecular pathways regulated by P4-PR in the mouse uterus, Affymetrix MG U74Av2 oligonucleotide arrays were used to identify alterations in gene expression after acute and chronic P4 treatments. In the analysis, retinoic acid metabolic genes, cytochrome P 450 26a1 (Cyp26a1), alcohol dehydrogenase 5, and aldehyde dehydrogenase 1a1 (Aldh1a1); kallikrein genes, Klk5 and Klk6; and specific transcription factors, GATA-2 and Cited2 [cAMP-corticosterone-binding protein/p300-interacting transactivator with glutamic acid (E) and aspartic acid (D)-rich tail], were validated as regulated by the P4-PR axis. Identification and analysis of these responsive genes will help define the role of PR in regulating uterine biology.
2012-08-07 | GSE39920 | GEO