Effect of PDCD11 silencing on gene expression in MDA-MB-231 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE275527 | GEO | 2025/05/14
REPOSITORIES: GEO
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Project description:Microarrays analysis identifies WNT16in senescent fibroblasts. To identify genes expressed in replicative senescence, microarray experiments were conducted in which we compared the RNA expression profile of young MRC5 fibroblasts at population doubling 28 (PDL28) and replicative senescent MRC5 fibroblasts at PDL63. In total, 177 gene probes were upregulated and 338 gene probes were downregulated in senescent versus young MRC5 fibroblasts. Genes were classified based on mapping to KEGG pathways. Upregulated genes were enriched in three KEGG pathways, the Wingless-type MMTV integration site (WNT) signaling pathway (WNT16, PLCB4, CCND2, SFRP1, WNT5B, RAC2), cytokine-cytokine receptor interaction (TNFRSF10D, TNFRSF10B, TNFRSF10C, IL1R2, IL18, VEGFC), and the p53 signaling pathway (CDKN1A, TNFRSF10B, PERP, STEAP3, ZMAT3). Repressed genes were enriched in three KEGG pathways, cell cycle (PKMYT1, CDC7, CCNE2, MCM4, BUB1, CDC25A, CDKN1B, MCM6, PLK1, CDKN2C, CCNB2, MCM3, BUB1B, CCNA2, CDC2), cytokine-cytokine receptor interaction (KITLG, IL11, TNFSF4, CCL2, PDGFRA, TNFRSF11B, TGFBR1, IL1R1, TNFRSF19), and DNA replication (POLE, RFC2, MCM4, RNASEH2B, POLA1, DNA2, MCM6, PRIM1, RFC4, MCM3). Along with p53 transcriptional targets (CDKN1A, PERP, WIG1), genes encoding secreted factors (WNT16, MMP10, MMP3) were among the most strongly increased in senescent cells.
2009-12-15 | GSE15919 | GEO
Project description:Microarrays analysis identifies WNT16in senescent fibroblasts. To identify genes expressed in replicative senescence, microarray experiments were conducted in which we compared the RNA expression profile of young MRC5 fibroblasts at population doubling 28 (PDL28) and replicative senescent MRC5 fibroblasts at PDL63. In total, 177 gene probes were upregulated and 338 gene probes were downregulated in senescent versus young MRC5 fibroblasts. Genes were classified based on mapping to KEGG pathways. Upregulated genes were enriched in three KEGG pathways, the Wingless-type MMTV integration site (WNT) signaling pathway (WNT16, PLCB4, CCND2, SFRP1, WNT5B, RAC2), cytokine-cytokine receptor interaction (TNFRSF10D, TNFRSF10B, TNFRSF10C, IL1R2, IL18, VEGFC), and the p53 signaling pathway (CDKN1A, TNFRSF10B, PERP, STEAP3, ZMAT3). Repressed genes were enriched in three KEGG pathways, cell cycle (PKMYT1, CDC7, CCNE2, MCM4, BUB1, CDC25A, CDKN1B, MCM6, PLK1, CDKN2C, CCNB2, MCM3, BUB1B, CCNA2, CDC2), cytokine-cytokine receptor interaction (KITLG, IL11, TNFSF4, CCL2, PDGFRA, TNFRSF11B, TGFBR1, IL1R1, TNFRSF19), and DNA replication (POLE, RFC2, MCM4, RNASEH2B, POLA1, DNA2, MCM6, PRIM1, RFC4, MCM3). Along with p53 transcriptional targets (CDKN1A, PERP, WIG1), genes encoding secreted factors (WNT16, MMP10, MMP3) were among the most strongly increased in senescent cells. Six arrays were hybridized with complex probes consisting of RNA isolated from MRC5 fibroblasts at population doubling 63 (undergoing replicative senescence) and RNA isolated from MRC5 fibroblats at population doubling 28 (young). The six arrays correspond to three biological replicates, each with a dye-swap technical replicate.
2010-05-18 | E-GEOD-15919 | biostudies-arrayexpress
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2023-03-10 | PXD034222 | Pride
Project description:In the first trimester of pregnancy the human placenta grows rapidly, making it sensitive to changes in the intrauterine environment. To test whether exposure to an environment in utero often associated with obesity modifies placental proteome and function, we performed untargeted proteomics (LC-MS/MS) in placentas from 19 women (gestational age 35–48 days, i.e. 5+0–6+6 weeks). Maternal clinical traits (body mass index, leptin, glucose, C-peptide and insulin sensitivity) and gestational age were recorded. DNA replication and cell cycle pathways were enriched in the proteome of placentas of women with low maternal insulin sensitivity. Driving these pathways were the minichromosome maintenance (MCM) proteins MCM2, MCM3, MCM4, MCM5, MCM6 and MCM7 (MCM-complex). These proteins are part of the pre-replicative complex and participate in DNA damage repair. Indeed, MCM6 and γH2AX (DNA-damage marker) protein levels correlated in first trimester placental tissue (r = 0.514, P<0.01). MCM6 and γH2AX co-localized to nuclei of villous cytotrophoblast cells, the proliferative cell type of the placenta, suggesting increased DNA damage in this cell type. To mimic key features of the intrauterine obesogenic environment, a first trimester trophoblast cell line, i.e., ACH-3P, was exposed to high insulin (10 nM) or low oxygen tension (2.5% O2). There was a significant correlation between MCM6 and γH2AX protein levels, but these were independent of insulin or oxygen exposure. These findings show that chronic exposure in utero to reduced maternal insulin sensitivity during early pregnancy induces changes in the early first trimester placental proteome. Pathways related to DNA replication, cell cycle and DNA damage repair appear especially sensitive to such an in utero environment.
2025-05-07 | PXD056380 | Pride
Project description:The controlled assembly of replication forks is critical for genome stability. The Dbf4-dependent Cdc7 kinase (DDK) initiates replisome assembly by phosphorylating the MCM2-7 replicative helicase at the N-terminal tails of Mcm2, Mcm4 and Mcm6. At present, it remains poorly understood how DDK docks onto the helicase and how the kinase targets distal Mcm subunits for phosphorylation. By cryo-electron microscopy and biochemical analysis we discovered that an interaction between the HBRCT domain of Dbf4 with Mcm2 serves as an anchoring point, which supports binding of DDK across the MCM2-7 double-hexamer interface and phosphorylation of Mcm4 on the opposite hexamer. Moreover, a rotation of DDK along its anchoring point allows phosphorylation of Mcm2 and Mcm6 on opposite hexamers. In summary, our work provides fundamental insights in the DDK structure, control and the selective activation of the MCM2-7 helicase during DNA replication, which can be exploited for development of novel DDK inhibitors.
2022-05-31 | PXD031315 | Pride
Project description:We tested if the changes in cell invasion and migration observed after MCM7 depletion manifested in an altered gene expression profile. For this purpose, we performed RNAseq analysis after MCM7 knock-down in A549 and A375 cells expressing a Dox-inducible shMCM7. As controls, we used shMCM7 cells that had not been induced with Dox, as well as the parental A549 and A375 cell lines grown in the presence or absence of Dox. To exclude possible effects caused by changes in cell cycle progression, all RNA samples were extracted from double thymidine synchronized cell populations, in which >98% cells were arrested at the G1/S phase boundary.
2021-01-01 | GSE149523 | GEO
Project description:T-cell intracellular antigen-1 (TIA1) is an RNA-binding protein modulating many regulatory aspects of target mRNA metabolism. Despite several reports referring to the role of TIA1 in carcinogenesis, little is known about the significance of its expression and function in human cancers including esophageal squamous cell carcinoma (ESCC). In the present study, we found that ectopic localization of overexpressed TIA1 in the cytoplasm was observed in a cohort of 143 ESCC patients using immunohistochemistry, and the cytoplasmic TIA1 was an independent prognosticator for worse overall survival. Moreover, we revealed that TIA1 was overexpression in many ESCC cell lines, and silencing of TIA1 in those cells inhibited cell growth with an accumulation of cells in G0–G1 and sub-G1 phases. The human TIA1 gene generates two major protein isoforms, TIA1a and TIA1b. Expression of TIA1a isoform tended to be higher than that of TIA1b in ESCC cells, and TIA1a was expressed both in the nucleus and cytoplasm but TIA1b was expressed mainly in the nucleus. Further studies revealed that each isoform showed opposite effects on cell proliferation through ectopically introducing each gene: TIA1a promotes anchorage-dependent and independent cell proliferation, whereas TIA1b inhibits cell proliferation and/or induces cell death. The ribonucleoprotein immunoprecipitation followed by a microarray analysis or massive-parallel sequencing identified a set of TIA1-associating mRNAs including enriched cell cycle-associated genes. Among them, SKP2 and CCNA2 mRNA were shown to be interacted with TIA1 protein through their different regions, and SKP2 and CCNA2 protein levels were positively regulated by TIA1 through suppression of mRNA decay and translational induction, respectively. These findings provide new insights into the previously unknown role of TIA1 and its isoforms as tumor-promoting molecules regulating a set of downstream oncogenic proteins, and implicate their potential application as a useful marker of malignant potential and a therapeutic target in ESCC.
2016-03-31 | GSE71342 | GEO
Project description:T-cell intracellular antigen-1 (TIA1) is an RNA-binding protein modulating many regulatory aspects of target mRNA metabolism. Despite several reports referring to the role of TIA1 in carcinogenesis, little is known about the significance of its expression and function in human cancers including esophageal squamous cell carcinoma (ESCC). In the present study, we found that ectopic localization of overexpressed TIA1 in the cytoplasm was observed in a cohort of 143 ESCC patients using immunohistochemistry, and the cytoplasmic TIA1 was an independent prognosticator for worse overall survival. Moreover, we revealed that TIA1 was overexpression in many ESCC cell lines, and silencing of TIA1 in those cells inhibited cell growth with an accumulation of cells in G0âG1 and sub-G1 phases. The human TIA1 gene generates two major protein isoforms, TIA1a and TIA1b. Expression of TIA1a isoform tended to be higher than that of TIA1b in ESCC cells, and TIA1a was expressed both in the nucleus and cytoplasm but TIA1b was expressed mainly in the nucleus. Further studies revealed that each isoform showed opposite effects on cell proliferation through ectopically introducing each gene: TIA1a promotes anchorage-dependent and independent cell proliferation, whereas TIA1b inhibits cell proliferation and/or induces cell death. The ribonucleoprotein immunoprecipitation followed by a microarray analysis or massive-parallel sequencing identified a set of TIA1-associating mRNAs including enriched cell cycle-associated genes. Among them, SKP2 and CCNA2 mRNA were shown to be interacted with TIA1 protein through their different regions, and SKP2 and CCNA2 protein levels were positively regulated by TIA1 through suppression of mRNA decay and translational induction, respectively. These findings provide new insights into the previously unknown role of TIA1 and its isoforms as tumor-promoting molecules regulating a set of downstream oncogenic proteins, and implicate their potential application as a useful marker of malignant potential and a therapeutic target in ESCC. To investigate the target molecules regulated by TIA1 in esophageal squamous cell carcinoma cell line (KYSE180), the expression levels of mRNAs (total) and transcripts captured by RIP with TIA1 antibody (TIA1_RIP) were analyzed using microarray.
2016-03-31 | E-GEOD-71342 | biostudies-arrayexpress
Project description:In T-cell acute lymphoblastic leukemia (T-ALL) NOTCH 1 receptors are frequently mutated. This leads to aberrantly high Notch signaling, but how this translates into deregulated cell cycle control and the transformed cell type is poorly understood. In this report, we analyze downstream responses resulting from the high level of NOTCH 1 signaling in T-ALL. Notch activity, measured immediately downstream of the NOTCH 1 receptor, is high, but expression of the canonical downstream Notch response genes HES 1 and HEY 2 is low both in primary cells from T-ALL patients and in T-ALL cell lines. This suggests that other immediate Notch downstream genes are activated, and we found that Notch signaling controls the levels of expression of the E3 ubiquitin ligase SKP2 and its target protein p27Kip1. We show that in T-ALL cell lines, recruitment of NOTCH 1 ICD to the SKP2 promoter was accompanied by high SKP2 and low p27Kip1 protein levels were low. In contrast, pharmacologically blocking Notch signaling reversed this picture and led to loss of NOTCH 1 ICD occupancy of the SKP2 promoter, decreased SKP2 and increased p27Kip1 expression. T-ALL cells show a rapid G1-S cell cycle transition, while blocked Notch signaling resulted in G0/G1 cell cycle arrest, also observed by transfection of p27Kip1 or, to a smaller extent, a dominant negative SKP2 allele. Collectively, our data suggest that the aberrantly high Notch signaling in T-ALL maintains SKP2 at a high level and reduces p27Kip1, which leads to more rapid cell cycle progression. Keywords: comparative genomic hybridization
2006-12-15 | GSE6495 | GEO
Project description:In T-cell acute lymphoblastic leukemia (T-ALL) NOTCH 1 receptors are frequently mutated. This leads to aberrantly high Notch signaling, but how this translates into deregulated cell cycle control and the transformed cell type is poorly understood. In this report, we analyze downstream responses resulting from the high level of NOTCH 1 signaling in T-ALL. Notch activity, measured immediately downstream of the NOTCH 1 receptor, is high, but expression of the canonical downstream Notch response genes HES 1 and HEY 2 is low both in primary cells from T-ALL patients and in T-ALL cell lines. This suggests that other immediate Notch downstream genes are activated, and we found that Notch signaling controls the levels of expression of the E3 ubiquitin ligase SKP2 and its target protein p27Kip1. We show that in T-ALL cell lines, recruitment of NOTCH 1 ICD to the SKP2 promoter was accompanied by high SKP2 and low p27Kip1 protein levels were low. In contrast, pharmacologically blocking Notch signaling reversed this picture and led to loss of NOTCH 1 ICD occupancy of the SKP2 promoter, decreased SKP2 and increased p27Kip1 expression. T-ALL cells show a rapid G1-S cell cycle transition, while blocked Notch signaling resulted in G0/G1 cell cycle arrest, also observed by transfection of p27Kip1 or, to a smaller extent, a dominant negative SKP2 allele. Collectively, our data suggest that the aberrantly high Notch signaling in T-ALL maintains SKP2 at a high level and reduces p27Kip1, which leads to more rapid cell cycle progression. Experiment Overall Design: Three independent cultures of the MOLT4 cell line before and 48 hours after addition of the gamma-secretase inhibitor DAPT (5 uM).
2008-06-14 | E-GEOD-6495 | biostudies-arrayexpress