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Homo sapiens

ABSTRACT: RNA-Sequencing of human papillary thyroid carcinomas

OTHER RELATED OMICS DATASETS IN: E-GEOD-64912

PROVIDER: PRJNA272493 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1754120_1.fastq.gz	Fastqsanger.gz
	SRR1754120_2.fastq.gz	Fastqsanger.gz
	SRR1754130_1.fastq.gz	Fastqsanger.gz
	SRR1754130_2.fastq.gz	Fastqsanger.gz
	SRR1754121_1.fastq.gz	Fastqsanger.gz

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E-GEOD-64912

Project description:RNA-Sequencing of human papillary thyroid carcinomas

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PIAS2b dsRNAi repression kills by mitotic catastrophe anaplastic thyroid and non-thyroid carcinomas, but not normal thyroid or differentiated carcinomas

Project description:The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with very high mortality. Double-stranded RNA–directed RNA interference (dsRNAi) targeting the PIAS2 isoform beta (PIAS2b) inhibits growth of ATC cell lines and patient primary cultures in vitro and orthotopic patient-derived xenografts (oPDX) in vivo, but not of thyroid cell lines or non-anaplastic primary thyroid cultures (differentiated carcinoma, benign lesions, or normal). PIAS2b-dsRNAi also has an anti-cancer effect on other anaplastic human cancers (pancreas, lung, and gastric). Mechanistically, PIAS2b is required for proper mitotic spindle and centrosome assembly, and it is a dosage-sensitive protein in ATC. Strikingly, PIAS2b-dsRNAi induces mitotic catastrophe at prophase. High-throughput proteomics revealed the proteasome (PSMC5) and spindle cytoskeleton as direct targets of PIAS2b SUMOylation at mitotic initiation. PIAS2b-dsRNAi is a promising therapy for ATC and other aggressive anaplastic cancers.

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