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In vivo CRISPR screen identifies SNRPC as a regulator for facilitating triple-negative breast cancer progression

ABSTRACT: In vivo CRISPR screen identifies SNRPC as a regulator for facilitating triple-negative breast cancer progression

PROVIDER: PRJNA943537 | ENA |

REPOSITORIES: ENA

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In vivo CRISPR screen identifies SNRPC as a regulator for facilitating triple-negative breast cancer progression [RNA-Seq]

Project description:In this study, we employed an in vivo CRISPR screening and a TNBC progression model to identify potentially oncogenic RBPs. We identified the small nuclear ribonucleoprotein polypeptide C (SNRPC), a subunit of the U1 small nuclear ribonucleoprotein particle (U1 snRNP), as a key modulator involved in TNBC progression. SNRPC was frequently upregulated and relevant to poor prognosis in TNBC patients. SNRPC ablation significantly impaired the proliferation, migration and invasion of TNBC cells in vitro and in vivo. In addition, SNRPC was essential for the stability of U1 snRNP and contributed to the RNA Pol II-controlled transcription program. Knockdown of SNRPC decreased RNA Pol II enrichment on some oncogenes (TNFAIP2, E2F2 and CDK4) and reduced their expression levels. We further confirmed that SNRPC deletion would inhibit TNBC progression partially through the TNFAIP2-Rac1-β-catenin signal.

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In vivo CRISPR screen identifies SNRPC as a regulator for facilitating triple-negative breast cancer progression [ChIP-Seq]

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Project description:Emerging evidence suggests that tumor cells metastasize by co-opting stem cell transcriptional networks, although the molecular underpinnings of this process are poorly understood. Here, we show for the first time that the high mobility group A1 (HMGA1) gene drives metastatic progression in triple negative breast cancer cells (MDA-MB-231) by reprogramming cancer cells to a stem-like state. We discovered an HMGA1 signature in triple negative breast cancer cells that is highly enriched in embryonic stem cells. Together, these findings indicate that HMGA1 is a master regulator of tumor progression in breast cancer by reprogramming cancer cells through stem cell transcriptional networks. Future studies are needed to determine how to target HMGA1 in therapy. HMGA1 was knocked-down in MDA-MB-231 cells using siRNA as we previously described (Tesfaye A 2007). RNA from three independent knockdown experiements along with 3 control populations were collected by Rneasy miniprep (Qiagen) and analyzed by Affymetrix Human Exon 1.0 ST platform.

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Project description:RBP-CRISPR Plasmid data of "In vivo CRISPR screen identifies SNRPC as a regulator for facilitating triple-negative breast cancer progression"

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In vivo CRISPR screen identifies SNRPC as a regulator for facilitating triple-negative breast cancer progression

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-03-15 | GSE227188 | GEO

HMGA1: A master regulator of tumor progression in triple-negative breast cancer cells

2015-02-18 | GSE45483 | GEO

Project description:CHIP-seq data of Project identifying SNRPC as a regulator for facilitating triple-negative breast cancer progression

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