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Multileveled reduction of p21 expression by Linc-ASEN represses cellular senescence

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE128398 | GEO | 2019/09/24

REPOSITORIES: GEO

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A novel long noncoding RNA Linc-ASEN represses cellular senescence through multileveled reduction of p21 expression.

Project description: Not available

| S-EPMC7244501 | biostudies-literature

Multileveled reduction of p21 expression by Linc-ASEN represses cellular senescence [ChIRP-seq]

Project description:Long noncoding RNAs regulating diverse cellular processes implicate in many diseases. Here, we report the identification of a novel long intergenic noncoding RNA, Linc-ASEN, expressed in prematurely senescent cells, that associates with UPF1 and represses cellular senescence by reducing p21 production transcriptionally and post-transcriptionally. The Linc-ASEN-UPF1 complex suppressed p21 transcription by recruiting Polycomb Repressive Complex 1 (PRC1) and PRC2 to the p21 locus, and thereby preventing binding of the transcriptional activator p53 on the p21 promoter. Moreover, the Linc-ASEN-UPF1 complex repressed p21 expression post-transcriptionally by lowering p21 mRNA stability in association with DCP1A. Accordingly, Linc-ASEN levels were found inversely correlated with p21 mRNA levels in tumor tissues from patient-derived xenograft mice, in various human cancer tissues, and in aged mice tissues. Our studies reveal that Linc-ASEN prevents cellular senescence by reducing the transcription and stability of p21 mRNA in concert with UPF1, and suggest that Linc-ASEN might be a potential therapeutic target in processes influenced by senescence, including cancer.

2019-09-24 | GSE128396 | GEO