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RNA-Seq analysis RPE1 cells following exposure to Nutlin-3 to identify target genes of p53 [tpo12]

ABSTRACT: Tetraploidization, or genome doubling, is a prominent event in tumorigenesis, primarily because cell division in polyploid cells is error-prone and produces aneuploid cells. This study investigates changes in gene expression evoked in acute and adapted tetraploid cells and their impact on cell-cycle progression. Acute polyploidy was generated by knockdown of essential regulator of cytokinesis Anillin, which resulted in cytokinesis failure and formation of binucleate cells, or by chemical inhibition of Aurora kinases, causing abnormal mitotic exit with formation of single cells with aberrant nuclear morphology. Transcriptome analysis of these acute tetraploid cells revealed common signatures of activation of the tumor-suppressor protein p53. Suppression of proliferation in these cells was dependent on p53 and its transcriptional target - Cdk inhibitor p21. Rare proliferating tetraploid cells can emerge from acute polyploid populations. Gene expression analysis of single-cell derived, adapted tetraploid clones showed upregulation of several p53 target genes and cyclin D2, the activator of Cdk4/6/2. Overexpression of cyclin D2 in diploid cells strongly potentiated the ability to proliferate with increased DNA content despite the presence of functional p53. These results point out that p53-mediated suppression of proliferation of polyploid cells can be averted by increased levels of oncogenes such as Cyclin D2, elucidating a possible route for tetraploidy-mediated genomic instability in carcinogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE86104 | GEO | 2016/09/01

SECONDARY ACCESSION(S): PRJNA340264

REPOSITORIES: GEO

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RNA-Seq analysis of proliferating 4N and 2N RPE1 cells derived from single cell clones following inhibition of Aurora B to induce polyploidization [tpo10]

Project description:Tetraploidization, or genome doubling, is a prominent event in tumorigenesis, primarily because cell division in polyploid cells is error-prone and produces aneuploid cells. This study investigates changes in gene expression evoked in acute and adapted tetraploid cells and their impact on cell-cycle progression. Acute polyploidy was generated by knockdown of essential regulator of cytokinesis Anillin, which resulted in cytokinesis failure and formation of binucleate cells, or by chemical inhibition of Aurora kinases, causing abnormal mitotic exit with formation of single cells with aberrant nuclear morphology. Transcriptome analysis of these acute tetraploid cells revealed common signatures of activation of the tumor-suppressor protein p53. Suppression of proliferation in these cells was dependent on p53 and its transcriptional target - Cdk inhibitor p21. Rare proliferating tetraploid cells can emerge from acute polyploid populations. Gene expression analysis of single-cell derived, adapted tetraploid clones showed upregulation of several p53 target genes and cyclin D2, the activator of Cdk4/6/2. Overexpression of cyclin D2 in diploid cells strongly potentiated the ability to proliferate with increased DNA content despite the presence of functional p53. These results point out that p53-mediated suppression of proliferation of polyploid cells can be averted by increased levels of oncogenes such as Cyclin D2, elucidating a possible route for tetraploidy-mediated genomic instability in carcinogenesis.

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Gene expression profile of diploid and tetraploid mouse primary hepatocyte

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2017-02-10 | GSE57769 | GEO

Homo sapiens

Project description:RNA-Seq analysis of 4N and 2N RPE1 cells following polyploid induction via cytokinesis failure by siRNA knockdown of Anillin [tpo8]

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Transcriptome analysis of tetraploid cells identifies Cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53

Project description:Transcriptome analysis of tetraploid cells identifies Cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53

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Project description:Both diploid RPE-1 and BJ-1 cells were made tetraploid by transient treatment with the cytokinesis inhibitor DCD. Proliferating tetraploids from both BJ-1 and RPE-1 were selected and isolated. The gene expression profiles of the proliferating tetraploid cells were then compared to the diploids from which they originated.

2014-05-22 | GSE57864 | GEO

Gene expression in diploid and evolved tetraploid RPE-1 and BJ-1 cells

2014-05-22 | E-GEOD-57864 | biostudies-arrayexpress

Valproic acid achieves its anticancer activity by re-expression of cyclin D2

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The effect of aneuploidy on gene expression

Project description:Analysis of the gene expression changes observed in aneuploid b1 integrin YYFF MEFs generated as a result of repeated cytokinesis failure compared to tetraploid wild-type MEFs or tetraploid b1YYFF integrin MEFs. The results reveal aneuploidy-specific gene expression changes, both up-and downregulated genes uniquely detected in the aneuploid MEFs.

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