The tumor suppressor p53 transcriptionally activates target genes to suppress cellular proliferation during stress. p53 has also been implicated in the repression of the proto-oncogene Myc, but the mechanism has remained unclear. Here, we identify Pvt1b, a p53-dependent isoform of the long noncoding RNA (lncRNA) Pvt1, expressed 50 kb downstream of Myc, which becomes induced by DNA damage or oncogenic signaling and accumulates near its site of transcription. We show that production of the Pvt1b RNA is necessary and sufficient to suppress Myc transcription in cis without altering the chromatin organization of the locus. Inhibition of Pvt1b increases Myc levels and transcriptional activity and promotes cellular proliferation. Furthermore, Pvt1b loss accelerates tumor growth, but not tumor progression, in an autochthonous mouse model of lung cancer. These findings demonstrate that Pvt1b acts at the intersection of the p53 and Myc transcriptional networks to reinforce the anti-proliferative activities of p53.

中文翻译：

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p53激活长非编码RNA Pvt1b抑制Myc并抑制肿瘤发生。

肿瘤抑制因子p53转录激活靶基因，从而抑制应激过程中的细胞增殖。p53也与原癌基因Myc的抑制有关，但机制尚不清楚。在这里，我们确定Pvt1b，长非编码RNA（lncRNA）Pvt1的p53依赖性同种型，在Myc下游表达50 kb，它被DNA损伤或致癌信号所诱导，并在其转录位点附近积累。我们表明，Pvt1b RNA的产生是必要且足以抑制顺式Myc转录而不会改变基因座的染色质组织。抑制Pvt1b可增加Myc水平和转录活性，并促进细胞增殖。此外，Pvt1b丢失加速了肺癌的本地小鼠模型中的肿瘤生长，而不是肿瘤的进展。