Expression data from Pin1 inhibitor ATRA and Pin1 knockdown
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE63059 | GEO | 2015/04/12
SECONDARY ACCESSION(S): PRJNA266532
REPOSITORIES: GEO
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Project description:ATRA was identified as a Pin1 inhibitor via fluorescence polarization-based high throughput screening. We performed microarray expression profiling to demonstrate the similarity between ATRA and Pin1 KD at the genome-wide level APL NB4 cells in response to ATRRA or inducible Pin1 knockdown for 3 days were collected for RNA extraction and hybridization on Affymetrix microarrays. We sought to validate in genome-wide level whether similarity occurred between ATRA and Pin1 knockdown-treated NB4 cells.
2015-04-12 | E-GEOD-63059 | biostudies-arrayexpress
Project description:Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination safely cures fatal acute promyelocytic leukemia, but the mechanisms underlying their action and synergy remain elusive. ATRA inhibits APL, breast and liver cancers by targeting isomerase Pin1, a master regulator of oncogenic signaling. Here we show that ATO targets Pin1 and cooperates with ATRA to exert potent anticancer activity. ATO inhibits and degrades Pin1, and suppresses its oncogenic function by noncovalent binding to Pin1’s active site. ATRA increases cellular ATO uptake through upregulating aquaporin-9. ATO and ATRA, at clinically safe doses, cooperatively ablate Pin1 to block numerous cancer-driving pathways and inhibit the growth of triple-negative breast cancer cells and tumor-initiating cells in cell and animal models including patient-derived orthotopic xenografts, similar to Pin1 CRISPR knockout, which is substantiated by comprehensive protein and microRNA analyses. Thus, synergistic Pin1 inhibition by ATO and ATRA offers an attractive approach to combating breast and other cancers.
2018-08-20 | GSE116264 | GEO
Project description:Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination safely cures fatal acute promyelocytic leukemia, but the mechanisms underlying their action and synergy remain elusive. ATRA inhibits APL, breast and liver cancers by targeting isomerase Pin1, a master regulator of oncogenic signaling. Here we show that ATO targets Pin1 and cooperates with ATRA to exert potent anticancer activity. ATO inhibits and degrades Pin1, and suppresses its oncogenic function by noncovalent binding to Pin1’s active site. ATRA increases cellular ATO uptake through upregulating aquaporin-9. ATO and ATRA, at clinically safe doses, cooperatively ablate Pin1 to block numerous cancer-driving pathways and inhibit the growth of triple-negative breast cancer cells and tumor-initiating cells in cell and animal models including patient-derived orthotopic xenografts, similar to Pin1 CRISPR knockout, which is substantiated by comprehensive protein and microRNA analyses. Thus, synergistic Pin1 inhibition by ATO and ATRA offers an attractive approach to combating breast and other cancers.
2018-10-16 | PXD010224 | Pride
Project description:The peptidyl-prolyl isomerase, Pin1, is exploited in cancer to activate oncogenes and inactivate tumor suppressors. However, despite considerable efforts, Pin1 has remained an elusive drug target. Here, we screened an electrophilic fragment library to identify covalent inhibitors targeting Pin1’s active site Cys113, leading to the development of Sulfopin, a nanomolar Pin1 inhibitor. Sulfopin is highly selective, as validated by two independent chemoproteomics methods, achieves potent cellular and in vivo target engagement, and phenocopies Pin1 genetic knockout. Pin1 inhibition had only a modest effect on cancer cell line viability. Still, Sulfopin induced downregulation of c-Myc target genes, reduced tumor progression and conferred survival benefit in murine and zebrafish models of MYCN-driven neuroblastoma, and in a murine model of pancreatic cancer. Our results demonstrate that Sulfopin is a suitable chemical probe for assessing Pin1-dependent pharmacology in cells and in vivo, and that Pin1 warrants further investigation as a potential cancer drug target.
2021-04-01 | GSE166786 | GEO
Project description:To discover the abnormal regulatory role of Pin1 in the ovarian cancer, The Pin1 full cDNA was knockIn (KI) the normal ovarian epithelium (Hose), and parallelly Pin1 was knockdown in the Ovarian cancer cells MCAS and sk-ov-3, and then compared the expression profiles of them to discovery the key features regulated by Pin1.
2018-01-04 | GSE84539 | GEO
Project description:To investigate the specific gene expression program by which mutant-p53 and Pin1 control invasion and metastasis in breast cancer cells, we compared the transcriptomic profile of control, mutant-p53 depleted or Pin1 depleted MDA-MB-231 cells.
2011-05-30 | GSE26262 | GEO
Project description:To investigate the specific gene expression program by which mutant-p53 and Pin1 control invasion and metastasis in breast cancer cells, we compared the transcriptomic profile of control, mutant-p53 depleted or Pin1 depleted MDA-MB-231 cells. MDA-MB-231 cells were transfected twice with siRNA against Pin1, p53 or LacZ as a control. Transfections were performed by using Lifofectamine 2000 (Invitrogen) according to manufacture's procedure. Forty-eight hours after second transfection, samples were then processed for total RNA extraction and hybridization on Affymetrix microarrays. Three biological replicas (A, B, C) were used for each of the three conditions, for a total of 9 samples
2011-05-30 | E-GEOD-26262 | biostudies-arrayexpress
Project description:Treatment of acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA) results in terminal differentiation of leukemic cells toward neutrophil granulocytes. Administration of ATRA leads to massive changes in gene expression, including down-regulation of cell proliferation-related genes and induction of genes involved in immune function. One of the most induced genes in APL NB4 cells is transglutaminase 2 (TG2). RNAi-mediated stable silencing of TG2 in NB4 cells (TG2-KD NB4) coupled with whole genome microarray analysis revealed that TG2 is involved in the expression of a large number of ATRA-regulated genes. The affected genes participate in granulocyte functions and their silencing lead to reduced adhesive, migratory and phagocytic capacity of neutrophils and less superoxide production. The expression of genes related to cell cycle control also changed, suggesting that TG2 regulates myeloid cell differentiation. CC chemokines CCL2, 3, 22, 24 and cytokines IL1B and IL8 involved in the development of differentiation syndrome (DS) are expressed at significantly lower levels in TG2-KD NB4 cells than in wild-type NB4 cells upon ATRA treatment. Based on our results, we propose that reduced expression of TG2 in differentiating APL cells may suppress effector functions of neutrophil granulocytes and attenuate the ATRA-induced inflammatory phenotype of DS. We used microarrays to detail the global program of gene expression underlying ATRA-induced differentiation of TG2 knockout NB4 cells. TG2 knockout NB4 cells were differentiated for 48 and 72 hours in the presence of ATRA and their gene expression profiles were compared to the wild-type cells at the same time points. Undifferentiated wild-type and TG2 knockout NB4 cells were used as untreated controls. Three biological replicates each.
2010-12-01 | E-GEOD-23702 | biostudies-arrayexpress
Project description:We report the development of rationally designed peptide inhibitors that covalently target Cys113, a highly conserved cysteine located in the Pin1 active site. The inhibitors were iteratively optimized for potency, selectivity, and cell permeability to give BJP-06-005-3, a versatile tool compound with which to probe Pin1 biology and interrogate its role in cancer, with the negative control compound BJP-06-115-3 (BJP-R). RNA-sequencing was performed to characterize the transcriptome-wide effects of 4h compound treatment.
2020-05-04 | GSE147340 | GEO
Project description:Treatment of acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA) results in terminal differentiation of leukemic cells toward neutrophil granulocytes. Administration of ATRA leads to massive changes in gene expression, including down-regulation of cell proliferation-related genes and induction of genes involved in immune function. One of the most induced genes in APL NB4 cells is transglutaminase 2 (TG2). RNAi-mediated stable silencing of TG2 in NB4 cells (TG2-KD NB4) coupled with whole genome microarray analysis revealed that TG2 is involved in the expression of a large number of ATRA-regulated genes. The affected genes participate in granulocyte functions and their silencing lead to reduced adhesive, migratory and phagocytic capacity of neutrophils and less superoxide production. The expression of genes related to cell cycle control also changed, suggesting that TG2 regulates myeloid cell differentiation. CC chemokines CCL2, 3, 22, 24 and cytokines IL1B and IL8 involved in the development of differentiation syndrome (DS) are expressed at significantly lower levels in TG2-KD NB4 cells than in wild-type NB4 cells upon ATRA treatment. Based on our results, we propose that reduced expression of TG2 in differentiating APL cells may suppress effector functions of neutrophil granulocytes and attenuate the ATRA-induced inflammatory phenotype of DS.
2010-12-01 | GSE23702 | GEO