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Analysis of gene expression in co-culture of PBMCs with ovarian cancer cell lines by High-Throughput Sequencing

ABSTRACT: (Objectives) The goal of this study is to investigate paracrine effect of peripheral blood mononuclear cells (PBMCs) on ovarian cancer cell lines. (Methods) Transcription profiles of PBMC (control) and PBMC co-cultured with ovarian cancer cell lines (treatment) were generated by deep sequencing, in triplicate, using Illumina HiSeq X Ten. (Results and Conclusions) Transcriptome analysis of PBMCs has revealed the expression change when co-cultured with EOC cell lines with significantly in up-regulated genes; CDKN1B, GIMAP8 and SNN. The qRT-PCR validation have indicated that GIMAP8 was high expressed in EOC patients when compared with healthy female. We summarized that PBMCs were changed their expression as a result of paracrine signals from ovarian cancer cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE110745 | GEO | 2020/12/31

REPOSITORIES: GEO

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Project description:Epithelial ovarian carcinoma (EOC) is an aggressive tumor often diagnosed at an advanced stage, when there is little prospect for cure. Despite some advances in surgical and chemotherapeutic strategies, only marginal improvements in patient outcome have been obtained. Hence, understanding the biological mechanisms underpinning EOC progression is critical for its treatment and to ameliorate patients survival. Recently, we reported that CD157 is expressed in EOC and controls tumor cell migration and invasion. Using stable overexpression and knockdown in OVCAR-3 and OV-90 ovarian cancer cell lines, we demonstrated that CD157 overexpression promotes morphological and functional changes, characterized by downregulation of epithelial marker and upregulation of mesenchymal ones. These are mediated at the transcriptional level by altering the expression of Snail and Zeb1 transcriptional repressors. The effects of CD157 overexpression on ovarian cancer phenotype translate into increased tumor cell motility and mesotelial invasion, while its knockdown significantly reduces the migratory potential, implying a direct correlation between CD157 expression levels and EOC aggressiveness. The analysis of the transcriptomic profiling highlighted 378 significantly differentially expressed genes, representing the signature of CD157-overexpressing EOC cells. The overall picture deduced from the analysis of these modulated transcripts indicated that high CD157 expression results in strengthening of a number of biological functions that favour tumor progression (including cell differentiation, cell motility and migration), and weakening of selected biological processes that hinder the tumor progression (such as apoptosis, cell death and response to stress). Collectively, these data support a causal role of CD157 in the control of ovarian cancer progression motivating the existence of a direct correlation between the expression levels of CD157 and the adverse clinical outcome in EOC patients, and suggest that CD157 may represent a valuable therapeutic target. Gene expression analysisi of control cell lines (OVCAR-3/mock and OV-90/mock) and testing cell lines (OVCAR-3/CD157 and OV-90/CD157), with two replicates, with dye swap, performed for each sample.

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Analysis of gene expression in co-culture of PBMCs with ovarian cancer cell lines by High-Throughput Sequencing

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