BMP4 induces a p21-dependent cell state shift in glioblastoma linking mesenchymal transition to senescence
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ABSTRACT:
PROVIDER: PRJNA1140857 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30011400_1.fastq.gz | Fastqsanger.gz | |||
| SRR30011400_2.fastq.gz | Fastqsanger.gz | |||
| SRR30011401_1.fastq.gz | Fastqsanger.gz | |||
| SRR30011401_2.fastq.gz | Fastqsanger.gz | |||
| SRR30011402_1.fastq.gz | Fastqsanger.gz |
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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.
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