Circular RNAs (circRNAs) are a class of noncoding RNAs produced by a noncanonical form of alternative splicing called back-splicing. To investigate a potential role of circRNAs in the p53 pathway, we analyzed RNA sequencing (RNA-seq) data from colorectal cancer cell lines (HCT116, RKO, and SW48) that were untreated or treated with a DNA-damaging agent. Surprisingly, unlike the strong p53-dependent induction of hundreds of p53-induced mRNAs upon DNA damage, only a few circRNAs were upregulated from p53-induced genes. circ-MDM2, an annotated circRNA from the MDM2 locus, was one of the handful of circRNAs that originated from a p53-induced gene. Given the central role of MDM2 in suppressing p53 protein levels and p53 activity, we investigated the function of circ-MDM2 Knocking down circ-MDM2 with small interfering RNAs (siRNAs) that targeted circ-MDM2 did not alter MDM2 mRNA or MDM2 protein levels but resulted in increased basal p53 levels and growth defects in vitro and in vivo Consistent with these results, transcriptome profiling showed increased expression of several direct p53 targets, reduced retinoblastoma protein (Rb) phosphorylation, and defects in G1-S progression upon silencing circ-MDM2 Our results on the initial characterization of circ-MDM2 identify a new player from the MDM2 locus that suppresses p53 levels and cell cycle progression.

中文翻译：

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来自MDM2基因座的环状RNA通过抑制p53水平来控制细胞周期进程。

环状RNA（circRNA）是一类非编码RNA，由非规范形式的选择性剪接（称为反向剪接）产生。为了研究circRNA在p53途径中的潜在作用，我们分析了未处理或未用DNA破坏剂处理过的结直肠癌细胞系（HCT116，RKO和SW48）的RNA测序（RNA-seq）数据。令人惊讶的是，与DNA损伤后数百种p53诱导的mRNA强烈依赖p53的诱导不同，p53诱导的基因仅上调了一些circRNA。circ-MDM2是来自MDM2基因座的带注释的circRNA，是少数源自p53诱导基因的circRNA之一。鉴于MDM2在抑制p53蛋白水平和p53活性方面的核心作用，