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The invasion promoter Slug is a critical cell cycle regulator

ABSTRACT: Background: The well-characterized function of the transcriptional repressor, Slug, is to promote EMT and tumor invasion/metastasis by down-regulating E-cadherin expression. In this study, we investigated the significance of Slug during the S phase. Method: Slug mRNA expression was isolated from thymidine-arrested CL1-5/AS2neo (control) and CL1-5/AS2neo-Slug-WT stable cells. The Agilent oligonucleotide microarray analysis was performed to identify Slug downstream genes. Results: Overexpression of Slug inhibited lung [3H]-thymidine incorporation and delayed S phase progression. By using Agilent microarray we have identified panel of genes altered by Slug overexpression. Slug can down-regulate target genes about cell cycle networks for DNA replication, DNA replication checkpoint and genomic stability, such as TOP1, ORC4, RFC3, and Rad17. Conclusions: the multifaceted role of Slug in cancer progression by controlling the epithelial-mesenchymal transition and genome stability.

ORGANISM(S): Homo sapiens

PROVIDER: GSE35617 | GEO | 2012/02/09

SECONDARY ACCESSION(S): PRJNA152455

REPOSITORIES: GEO

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The invasion promoter Slug is a critical cell cycle regulator

Project description:Background: The well-characterized function of the transcriptional repressor, Slug, is to promote EMT and tumor invasion/metastasis by down-regulating E-cadherin expression. In this study, we investigated the significance of Slug during the S phase. Method: Slug mRNA expression was isolated from thymidine-arrested CL1-5/AS2neo (control) and CL1-5/AS2neo-Slug-WT stable cells. The Agilent oligonucleotide microarray analysis was performed to identify Slug downstream genes. Results: Overexpression of Slug inhibited lung [3H]-thymidine incorporation and delayed S phase progression. By using Agilent microarray we have identified panel of genes altered by Slug overexpression. Slug can down-regulate target genes about cell cycle networks for DNA replication, DNA replication checkpoint and genomic stability, such as TOP1, ORC4, RFC3, and Rad17. Conclusions: the multifaceted role of Slug in cancer progression by controlling the epithelial-mesenchymal transition and genome stability. Two-condition experiment, Vector vs. Slug overexpression cells. The cDNAs encoding full-length human Slug were amplified and subcloned into lentiviral pLKO_AS2.neo which generated full-length Slug. Vector control or Slug lentivirus were transduced into CL1-5 cells and Gentamycin was used to select stable cells.

2012-02-09 | E-GEOD-35617 | biostudies-arrayexpress

Slug overexpression

Project description:This SuperSeries is composed of the following subset Series: GSE41026: Expression analysis of HepG2, HepG2-slug and HepG2-slug on Matrigel GSE41027: Chip-chip from HepG2 cells and HepG2 cells with slug overexpression Refer to individual Series

2012-09-21 | E-GEOD-41028 | biostudies-arrayexpress

Expression analysis of HepG2, HepG2-slug and HepG2-slug on Matrigel

2012-09-21 | GSE41026 | GEO

SLUG is enhanced by chemotherapeutics and functions to promote invasion and metastasis by directly targeting MMP3 in Cervical Cancer

Project description:Neoadjuvant chemotherapy (NACT) followed by radical surgery for patients in FIGO stages IB2-IIB has proven to reduce tumor volume and numbers. However, NACT followed by radical surgery has not been found to improve overall survival. In this study, 35 paired pre/post-NACT cervical cancer tissues and 167 cervical cancer samples were examined by immunohistochemical analysis, SLUG expression was potentially increased in cervical cancer tissues after neoadjuvant chemotherapy, which in turn positively correlated with pelvic lymph node metastasis. The expression of SLUG following neoadjuvant chemotherapy was identified as a poor survival indicator. Functional assays, Agilent microarray hybridization and CHIP assay were performed to determine SLUG’s downstream genes and pathways. SLUG overexpression promoted metastasis in cervical cancer in both in vitro and in vivo models, whereas SLUG silencing had the opposite effect. Mechanically, SLUG is not a prerequisite for EMT activation in cervical cancer models, but contributes to the invasiveness and metastasis of cervical cancer cells by directly tethering to the recognition sequence GCCAGGTGC in the MMP3 promoter region. Our results provide mechanistic insight into the potential pro-cancer effect of neoadjuvant chemotherapy, and demonstrates that the SLUG-MMP3 axis could serve as a target for improving the efficacy of chemotherapy.

2020-12-11 | GSE163002 | GEO

Expression analysis of HepG2, HepG2-slug and HepG2-slug on Matrigel

Project description:Investigation of whole genome gene expression level changes in hepatocellular carcinoma cell line hepG2 in regular culture, hepG2-slug in regular culture and hepG2-slug on Matrigel. Whole genome gene expression level changes have been compared in hepatocellular carcinoma cell line hepG2 in regular culture, hepG2-slug in regular culture and hepG2-slug on Matrigel. Roche NimbleGen micro-array analysis was employed to assess global genome expression in HepG2 in regular culture, HepG2-slug in regular culture and HepG2-slug on Matrigel. The results demonstrated that the up-regulated genes and the down-regulated genes increased significantly when HepG2-slug cells with VM forming ablity were cultured on Matrigel and formed VM.

2012-09-21 | E-GEOD-41026 | biostudies-arrayexpress

Slug-dependent UVR induction of cytokines and chemokines

Project description:Studies of the zinc finger transcription factors Slug and Snail have largely focused on their important role in modulating epithelial-mesenchymal transition during embryonic development and tumor progression. However, these transcription factors also appear to regulate local inflammation. In previous studies, we showed that Slug knockout mice were resistant to sunburn, an acute cutaneous inflammatory response, compared to wild type mice. In the present studies, we used Slug knockout, chimeric Slug knockout/wild type, conditional Slug knockout, and Slug transgenic mice to study the role of Slug in ultraviolet radiation (UVR)-induced cutaneous inflammation. We demonstrated, using immunohistochemistry, in vivo imaging, and neutrophil migration studies, that it was Slug expression in the epidermis rather than in neutrophils that modulated the UVR response. Microarray analysis indicated that this modulation was effected by the production of epidermal cytokines, including CCL3, CCL4, oncostatin, and interleukin-1β, that recruited neutrophils to UVR-exposed skin. The pattern of pro-inflammatory gene regulation by Slug suggested a central role for NF-κB in mediating gene induction. Immunohistochemical analysis of UVR-induced NF-κB activation demonstrated reduced activation in Slug knockout and enhanced activation in Slug transgenic epidermis. Slug thus appears to modulate NF-κB activation in response to UVR.

2016-08-27 | GSE86107 | GEO

Microarray transcriptome profiling of peripheral T-cell lymphomas in two groups differentiated by Twist and Slug protein expression

Project description:This experiment aimed to study the expression of the transcription factors Twist (TWIST1), ZEB1 and Slug (SNAI2) in peripheral T-cell lymphomas, and to see if these markers could be used to delineate lymphomas with different clinical outcomes and genetic profiles. Twist, ZEB1 and Slug expression was studied using immunohistochemistry in 67 Peripheral T-cell lymphomas and significant correlations to progression-free survival were found. Good prognosis group (high Twist, low Slug) and poor prognosis group (low Twist, high Slug) were formed for gene expression profiling. Microarray transcriptome analysis was performed on 12 cases (6 from each prognosis group) to evaluate differences in gene expression between the groups. Total RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue blocks using the RNeasy FFPE Kit (Qiagen, Hilden, Germany). Capillary electrophoresis was carried out to check the quality of RNA using the Agilent bioanalyzer and Agilent RNA 6000 Nano Kit (Agilent Technologies, Santa Clara, CA, USA). Transcriptome was analysed using GeneChip Human Gene ST Arrays (Affymetrix, Santa Clara, CA, USA) and the WT Pico Kit (Affymetrix Santa Clara, CA, USA) in accordance with the manufacturer’s instructions. Chipster CSC software (ver 3.11) was used to process the data files.

2019-08-30 | E-MTAB-6401 | biostudies-arrayexpress

Chip-chip from HepG2 cells and HepG2 cells with slug overexpression

Project description:The transcription factor slug represses genes with E-box and then activates cancer stem cell related pathway: Wnt, Notch and Hedgehog pathway. Chromatin immunoprecipitation (ChIP) of slug by ChIP-on-chip analysis demonstrated that slug indirectly activates cancer stem cell related pathway and thus promotes vasculogenic mimicry formation. Comparison of HepG2-control in regular culture, HepG2-slug in regular culture and HepG2-slug on Matrigel.

2012-09-21 | E-GEOD-41027 | biostudies-arrayexpress

Chip-chip from HepG2 cells and HepG2 cells with slug overexpression

2012-09-21 | GSE41027 | GEO

Slug-induced miR-137 expression contributes to non-small cell lung cancer progression

Project description:The epithelial-mesenchymal transition (EMT) regulator Slug has multifaceted roles in controlling lung cancer progression, but the downstream targets and underlying mechanisms of Slug remain undetermined. The miRNAs downstream of Slug in lung cancer cells were examined using Illumina bead arrays and TaqMan low-density arrays.

2017-01-01 | GSE84040 | GEO

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