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Oncogenic RAD21 Amplification Coordinates with YAP/TEAD Transcriptional Co-Repressor Complex to Drive Tumorigenesis in High Grade Serous Ovarian Cancer

ABSTRACT: Oncogenic RAD21 Amplification Coordinates with YAP/TEAD Transcriptional Co-Repressor Complex to Drive Tumorigenesis in High Grade Serous Ovarian Cancer

PROVIDER: PRJNA659364 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12515038.fastq.gz	Fastqsanger.gz
	SRR12515039.fastq.gz	Fastqsanger.gz
	SRR12515040.fastq.gz	Fastqsanger.gz
	SRR12515041.fastq.gz	Fastqsanger.gz
	SRR12515042.fastq.gz	Fastqsanger.gz

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Oncogenic RAD21 Amplification Coordinates with YAP/TEAD Transcriptional Co-Repressor Complex to Drive Tumorigenesis in High Grade Serous Ovarian Cancer

Project description:Ovarian cancer (OV) is the leading cause of mortality from gynaecological malignancies with poor prognosis and limited therapeutic options. Prevalent copy number alteration (CNA) is a genetic characteristic of OV, but its contribution to tumorigenesis remain unclear. Here, we identify RAD21, a component of the cohesin complex, as a frequently amplified and overexpressed oncogene in high grade serous ovarian cancer (HGSOC), the most common subtype of OV. RAD21 copy number amplification and overexpression are correlated with poor prognosis in HGSOC. In HGSOC cells and xenograft models, depletion of RAD21 inhibited cell proliferation by inducing mitotic phase arrest and thereby reducing tumour growth, whereas overexpression of RAD21 conferred resistance to carboplatin. Mechanistically, we found that RAD21 interacts with YAP/TEAD4 transcriptional co-repressors and recruits NuRD complex to suppress the downstream targets. Additionally, genetic and pharmacologic inhibition of YAP disrupts the co-repressor complex to suppress the oncogenic activity of RAD21 and recapitulates the phenotypes of RAD21 depletion in HGSOC. Therefore, our work sheds light on the oncogenic role of frequent CNAs and identifies a previously unrecognized role of RAD21/YAP complex which contributes to tumorigenesis and chemo-resistance in HGSOC.

2023-04-10 | GSE156845 | GEO

Oncogenic RAD21 Amplification Suppresses Interferon Signalling to Promote Immune Evasion in Ovarian Cancer

2023-04-10 | GSE193620 | GEO

Rad21

Project description:Rattus norvegicus Rad21, RAD21 cohesin complex component [Source:RGD Symbol;Acc:1594529], is differentially expressed in 23 experiment(s);

| ENSRNOG00000004420 | ExpressionAtlas

RAD21

Project description:Monodelphis domestica RAD21, RAD21 cohesin complex component [Source:NCBI gene;Acc:100025333], is expressed in 2 baseline experiment(s);

| ENSMODG00000004133 | ExpressionAtlas

Rad21

Project description:Rattus norvegicus Rad21, RAD21 cohesin complex component [Source:RGD Symbol;Acc:1594529], is expressed in 6 baseline experiment(s);

| ENSRNOG00000004420 | ExpressionAtlas

RAD21

Project description:Sus scrofa RAD21, RAD21 cohesin complex component [Source:VGNC Symbol;Acc:VGNC:92054], is expressed in 5 baseline experiment(s);

| ENSSSCG00000006014 | ExpressionAtlas

rad21

Project description:Xenopus tropicalis rad21, RAD21 cohesin complex component [Source:Xenbase;Acc:XB-GENE-1008099], is expressed in 1 baseline experiment(s);

| ENSXETG00000020783 | ExpressionAtlas

RAD21

Project description:Macaca mulatta RAD21, RAD21 cohesin complex component [Source:VGNC Symbol;Acc:VGNC:84108], is expressed in 3 baseline experiment(s);

| ENSMMUG00000020285 | ExpressionAtlas

RAD21

Project description:Homo sapiens RAD21, RAD21 cohesin complex component [Source:HGNC Symbol;Acc:HGNC:9811], is differentially expressed in 157 experiment(s);

| ENSG00000164754 | ExpressionAtlas

RAD21

Project description:Oryctolagus cuniculus RAD21, RAD21 cohesin complex component [Source:HGNC Symbol;Acc:HGNC:9811], is expressed in 1 baseline experiment(s);

| ENSOCUG00000002581 | ExpressionAtlas

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