Gene expression changes associated with reducing Sox2 expression in ovarian cancer cell line PA1 under anchorage independence
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA771387 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16345347.fastq.gz | Fastqsanger.gz | |||
| SRR16345348.fastq.gz | Fastqsanger.gz | |||
| SRR16345349.fastq.gz | Fastqsanger.gz | |||
| SRR16345350.fastq.gz | Fastqsanger.gz | |||
| SRR16345351.fastq.gz | Fastqsanger.gz |
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Project description:Sex-determining region Y- box 2 (Sox2) is a single-exon transcription factor essential for development and in cancer that has been shown to be overexpressed broadly in many cancers including multiple ovarian cancer subtypes. The objective of this study is to examine the effect of changing Sox2 expression under the conditions of anchorage independent growth that is known to drive the expression of survival genes. We compared genome wide gene expression profiles of the ovarian tumor cell line PA1 upon transient knockdown of Sox2 expression using siRNA and compared to negative silencer control siRNA cells. Cells grown in biological triplicates were transfected under steady state 2D growth conditions and then transferred to poly-hema coated plates to prevent attachment. After 72 hrs, RNA was collected from siSox2 and sicontrol cells followed by verification of reduction in Sox2 levels at the protein and RNA levels . Our analysis of the RNA seq results revealed 59 differentially expressed genes (DEG) between sicontrol and siSox2 cells (p-value ≤ 0.05) of which 52 were protein coding. Of the 59, 35 genes were upregulated in siSox2 and 24 genes were downregulated in the siSox2 cells . Gene set enrichment analysis of all the differentially expressed genes from the RNA-seq data revealed enrichment of 8 gene sets based on an FDR value <25% and included ‘hallmark of Apoptosis’, ‘TGF-β signaling’, and ‘Epithelial-Mesenchymal transition’ in siSox2 cells and hallmark interferon alpha response and interferon gamma response in sicontrol cells. Several transcription factors with prior established relationships to Sox2 including several PARP family members and TRIM family members were present in these gene sets.
2022-07-26 | GSE185932 | GEO
Project description:Acquisition of independence from anchorage to the extracellular matrix is a critical event for onset and progression of solid cancers. To identify and characterize new genes conferring anchorage independence, we transduced MCF10A human normal breast cells with a retroviral cDNA expression library and selected them by growth in suspension. Microarray analysis targeted on library-derived transcripts revealed robust and reproducible enrichment, after selection, of cDNAs encoding the scaffolding adaptor Gab2. Gab2 was confirmed to strongly promote anchorage-independent growth when overexpressed. Interestingly, downregulation by RNAi of endogenous Gab2 in neoplastic cells did not affect their adherent growth, but abrogated their growth in soft agar. Gab2-driven anchorage independence was found to specifically involve activation of the Src-Stat3 signaling axis. A transcriptional “signature” of 205 genes was obtained from GAB2-transduced, anchorage-independent MCF10A cells, and found to contain two main functional modules, respectively controlling proliferation and cell adhesion/migration/invasion. Extensive validation on breast cancer datasets showed that the Gab2-signature provides a robust prognostic classifier for breast cancer metastatic relapse, largely independent from existing clinical and genomic indicators and from estrogen receptor status. This work highlights a pivotal role for GAB2 and its transcriptional targets in anchorage-independent growth and breast cancer metastatic progression.
2009-10-21 | GSE18237 | GEO
Project description:Cervical cancer and a subset of anogenital and head-and-neck carcinomas are caused by persistent infection with high-risk types of the human papillomavirus (hrHPV). Early stages of hrHPV-induced carcinogenesis can be faithfully mimicked in vitro. A major hallmark of hrHPV-transformed cells is their ability to grow anchorage independently, an oncogenic trait known to depend on inactivation of tumour suppressor genes. This study used an in vitro model of hrHPV-induced transformation to delineate in a longitudinal manner to what extent DNA methylation-mediated silencing of tumour suppressive microRNAs (miRNAs) contributed to hrHPV-induced anchorage independence. Genome-wide miRNA expression profiles were yielded from anchorage dependent (n=11) and independent passages (n=19) of 4 hrHPV-immortalised keratinocyte cell lines with and without demethylating treatment (DAC). Unsupervised clustering analysis showed that overall miRNA expression patterns discriminated between anchorage dependent and independent cells. Ten miRNA genes potentially silenced by methylation were selected and validated by bisulfite sequencing and methylation-specific PCR. Hsa-mir-129-2, -137, -935, -3663, -3665, and -4281 showed increased methylation in both HPV-transformed keratinocytes and cervical cancer cell lines compared to primary keratinocytes. Mature miRNAs derived from hsa-mir-129-2, -137, -3663, and -3665 decreased anchorage independence in cervical cancer cell lines. Finally, significantly increased methylation of hsa-mir-129-2, -935, -3663, -3665, and -4281 was observed in cervical (pre)cancerous lesions, underlining the clinical relevance of our findings. In conclusion, methylation-mediated silencing of tumour suppressive miRNAs contributes to the acquisition of anchorage independence, supporting the importance of miRNAs during early stages of carcinogenesis and underlining their potential as both disease markers and therapeutic targets.
2017-02-09 | GSE78278 | GEO
Project description:Cervical cancer and a subset of anogenital and head-and-neck carcinomas are caused by persistent infection with high-risk types of the human papillomavirus (hrHPV). Early stages of hrHPV-induced carcinogenesis can be faithfully mimicked in vitro. A major hallmark of hrHPV-transformed cells is their ability to grow anchorage independently, an oncogenic trait known to depend on inactivation of tumour suppressor genes. This study used an in vitro model of hrHPV-induced transformation to delineate in a longitudinal manner to what extent DNA methylation-mediated silencing of tumour suppressive microRNAs (miRNAs) contributed to hrHPV-induced anchorage independence. Genome-wide miRNA expression profiles were yielded from anchorage dependent (n=11) and independent passages (n=19) of 4 hrHPV-immortalised keratinocyte cell lines with and without demethylating treatment (DAC). Unsupervised clustering analysis showed that overall miRNA expression patterns discriminated between anchorage dependent and independent cells. Ten miRNA genes potentially silenced by methylation were selected and validated by bisulfite sequencing and methylation-specific PCR. Hsa-mir-129-2, -137, -935, -3663, -3665, and -4281 showed increased methylation in both HPV-transformed keratinocytes and cervical cancer cell lines compared to primary keratinocytes. Mature miRNAs derived from hsa-mir-129-2, -137, -3663, and -3665 decreased anchorage independence in cervical cancer cell lines. Finally, significantly increased methylation of hsa-mir-129-2, -935, -3663, -3665, and -4281 was observed in cervical (pre)cancerous lesions, underlining the clinical relevance of our findings. In conclusion, methylation-mediated silencing of tumour suppressive miRNAs contributes to the acquisition of anchorage independence, supporting the importance of miRNAs during early stages of carcinogenesis and underlining their potential as both disease markers and therapeutic targets.
2017-02-09 | GSE78277 | GEO
Project description:Gene expression profiling in PA1 ovarian cancer cells under anchorage independence either in the presence of vehicle or BMP9 treatment for 24 hours
| PRJNA771377 | ENA
Project description:The detachment of epithelial cells, but not cancer cells, causes anoikis due to reduced energy production. Invasive tumor cells generate three splice variants of the metastasis gene osteopontin. The cancer-specific form osteopontin-c supports anchorage-independence through inducing oxidoreductases and upregulating intermediates/enzymes in the hexose monophosphate shunt, glutathione cycle, glycolysis, glycerol phosphate shuttle, and mitochondrial respiratory chain. Osteopontin-c signaling upregulates glutathione (consistent with the induction of the enzyme GPX-4), glutamine and glutamate (which can feed into the tricarboxylic acid cycle). Consecutively, the cellular ATP levels are elevated. The elevated creatine may be synthesized from serine via glycine and also supports the energy metabolism by increasing the formation of ATP. Metabolic probing with N-acetyl-L-cysteine, L-glutamate, or glycerol identified differentially regulated pathway components, with mitochondrial activity being redox dependent and the creatine pathway depending on glutamine. The effects are consistent with a stimulation of the energy metabolism that supports anti-anoikis. Our findings imply a synergism in cancer cells between osteopontin-a, which increases the cellular glucose levels, and osteopontin-c, which utilizes this glucose to generate energy.
2014-02-21 | GSE55193 | GEO
Project description:The detachment of epithelial cells, but not cancer cells, causes anoikis due to reduced energy production. Invasive tumor cells generate three splice variants of the metastasis gene osteopontin. The cancer-specific form osteopontin-c supports anchorage-independence through inducing oxidoreductases and upregulating intermediates/enzymes in the hexose monophosphate shunt, glutathione cycle, glycolysis, glycerol phosphate shuttle, and mitochondrial respiratory chain. Osteopontin-c signaling upregulates glutathione (consistent with the induction of the enzyme GPX-4), glutamine and glutamate (which can feed into the tricarboxylic acid cycle). Consecutively, the cellular ATP levels are elevated. The elevated creatine may be synthesized from serine via glycine and also supports the energy metabolism by increasing the formation of ATP. Metabolic probing with N-acetyl-L-cysteine, L-glutamate, or glycerol identified differentially regulated pathway components, with mitochondrial activity being redox dependent and the creatine pathway depending on glutamine. The effects are consistent with a stimulation of the energy metabolism that supports anti-anoikis. Our findings imply a synergism in cancer cells between osteopontin-a, which increases the cellular glucose levels, and osteopontin-c, which utilizes this glucose to generate energy. mRNA profiles of MCF-7 cells transfected with osteopontin-a, osteopontin-c and vector control were generated by RNA-Seq, in triplicate, by Illumina HiSeq.
2014-02-21 | E-GEOD-55193 | biostudies-arrayexpress
Project description:Aberrant methylation-mediated silencing of microRNAs contributes to HPV-induced anchorage independence
| PRJNA313079 | ENA
Project description:Sox2 has been studied in several types of human solid tumors. The investigators found that Sox2 had higher expression level in colorectal cancer and metastatic tissues than normal tissues. So the investigators assumed that whether Sox2 plays an important role in the progression and migration of colon cancer.
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Project description:PA1 has been identified as a component of a MLL3/4-containing histone methyltransferase complex. PA1 directly interacts with PTIP but not with other complex components. Since biological functions of PA1 are unknown, we used microarrays to determine which genes are regulated by PA1. To identify PA1-regulated genes, immortalized PA1 conditional knockout PA1loxP/loxP MEFs were infected with retroviruses expressing either Cre recombinase or vector alone. We prepared duplicated RNAs from either vector or Cre infected cells (PA1+/+ or PA1-/-) for 4 affymetrix microarrays.
2013-12-31 | E-GEOD-20157 | biostudies-arrayexpress