GSE128396
Multileveled reduction of p21 expression by Linc-ASEN represses cellular senescence [ChIRP-seq]
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. Overall design: Analysis of genome wide binding sites of Linc-ASEN via ChIRP-seq in MCF7 breast cancer cells.