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Targeting the mRNA endonuclease CPSF73 inhibits breast cancer cell migration and invasion

ABSTRACT: Targeting the mRNA endonuclease CPSF73 inhibits breast cancer cell migration and invasion

PROVIDER: PRJNA784278 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17055454_1.fastq.gz	Fastqsanger.gz
	SRR17055454_2.fastq.gz	Fastqsanger.gz
	SRR17055455_1.fastq.gz	Fastqsanger.gz
	SRR17055455_2.fastq.gz	Fastqsanger.gz
	SRR17055456_1.fastq.gz	Fastqsanger.gz

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Targeting the mRNA endonuclease CPSF73 inhibits breast cancer cell migration and invasion

Project description:Targeting the mRNA endonuclease CPSF73 inhibits breast cancer cell migration and invasion

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Targeting the mRNA endonuclease CPSF73 inhibits breast cancer cell migration and invasion

Project description:Cleavage by the endonuclease CPSF73 and polyadenylation of nascent RNA is an essential step in co-transcriptional mRNA maturation, and abnormal poly(A) site choices have been associated with human diseases, including cancer. Recent work has surprisingly identified CPSF73 as a promising drug target for inhibiting the growth of specific cancers. However, our understanding of the regulation of CPSF73 is still at an early stage. Here, we report that a HECT-like E3 ligase, UBE3D, participates in stabilizing CPFS73 protein by preventing its ubiquitin-mediated degradation by the proteasome. Depletion of UBE3D in both non-cancer cells and cancer cells leads to CPSF73 downregulation, a pre-mRNA cleavage defect and dysregulated gene expression. UBE3D dysfunction or chemical inactivation of CPFS73 inhibited migration and invasion as well as stem cell renewal phenotypes in vitro in triple negative breast cancer cells. Our findings indicate that targeting the pre-mRNA processing nuclease CPSF73 has potential for breast cancer therapy.

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Targeting the mRNA endonuclease CPSF73 inhibits breast cancer cell migration and invasion

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