Identification of new p53 target microRNAs by bioinformatics and functional analysis.
Identification of new p53 target microRNAs by bioinformatics and functional analysis.
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DOI：
10.1186/1471-2407-13-552
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发表时间：
2013-11-21
期刊：
影响因子：
3.8
通讯作者：
Ciribilli Y
中科院分区：
文献类型：
--
作者：
Bisio A;De Sanctis V;Del Vescovo V;Denti MA;Jegga AG;Inga A;Ciribilli Y
肿瘤抑制因子p53是一种序列特异性转录因子，它调节一个广泛的编码基因网络，长链非编码rna和microrna，这些基因建立复杂的基因调控回路，影响许多细胞反应，超出了细胞周期、细胞凋亡和DNA修复的典型控制。利用生物信息学方法，我们确定了p53直接转录控制下的另一组候选microrna （miRs）。为了验证p53家族介导的新预测目标miRs的应答性，我们首先使用一种基于酵母的检测方法，评估了野生型p53、p63β和p73β从miR启动子中定位的p53应答元件（REs）反激活的可能性。在miR-10b、-23b、-106a、-151a、-191、-198、-202、-221、-320、-1204、-1206启动子中发现的REs对p53有应答，其中8个启动子也对p63β或p73β有应答。还研究了种系p53突变在选定的mir相关REs中驱动转激活的可能性。在阿霉素处理的MCF7细胞和HCT116 p53+/+中进行的染色质免疫沉淀（ChIP）试验显示，p53在miR-202、-1204、-1206、-10b RE-containing位点适度诱导占据，而仅在MCF7细胞中观察到mir -23b相关RE的弱占据。RT-qPCR分析细胞显示，HCT116 p53+/+和MCF7细胞中成熟miR-10b， -23b， -151a水平的适度诱导依赖于阿霉素和/或nutlin。包含miR-1204和- 1206的长链非编码RNA PVT1仅在HCT116 p53+/+细胞中被弱诱导，但未检测到成熟的mir。在我们的细胞系统中，miR-202的表达不受p53激活刺激的影响。我们的研究揭示了其他miRs，特别是miR-10b和miR-151a，可以由p53家族转录因子直接调节，并有助于调节p53诱导的应答。
The tumor suppressor p53 is a sequence-specific transcription factor that regulates an extensive network of coding genes, long non-coding RNAs and microRNAs, that establish intricate gene regulatory circuits influencing many cellular responses beyond the prototypical control of cell cycle, apoptosis and DNA repair. Using bioinformatic approaches, we identified an additional group of candidate microRNAs (miRs) under direct p53 transcriptional control. To validate p53 family-mediated responsiveness of the newly predicted target miRs we first evaluated the potential for wild type p53, p63β and p73β to transactivate from p53 response elements (REs) mapped in the miR promoters, using an established yeast-based assay. The REs found in miR-10b, -23b, -106a, -151a, -191, -198, -202, -221, -320, -1204, -1206 promoters were responsive to p53 and 8 of them were also responsive to p63β or p73β. The potential for germline p53 mutations to drive transactivation at selected miR-associated REs was also examined. Chromatin Immuno-Precipitation (ChIP) assays conducted in doxorubicin-treated MCF7 cells and HCT116 p53+/+ revealed moderate induction of p53 occupancy at the miR-202, -1204, -1206, -10b RE-containing sites, while weak occupancy was observed for the miR-23b-associated RE only in MCF7 cells. RT-qPCR analyses cells showed modest doxorubicin- and/or Nutlin-dependent induction of the levels of mature miR-10b, -23b, -151a in HCT116 p53+/+ and MCF7 cells. The long noncoding RNA PVT1 comprising miR-1204 and −1206 was weakly induced only in HCT116 p53+/+ cells, but the mature miRs were not detected. miR-202 expression was not influenced by p53-activating stimuli in our cell systems. Our study reveals additional miRs, particularly miR-10b and miR-151a, that could be directly regulated by the p53-family of transcription factors and contribute to the tuning of p53-induced responses.
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影响因子：
64.8
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.
基于回归的预测因子p53反式激活。
影响因子：
3
作者：
Gowrisankar S;Jegga AG
通讯作者：
Jegga AG
影响因子：
11.2
作者：
Gabriely G;Yi M;Narayan RS;Niers JM;Wurdinger T;Imitola J;Ligon KL;Kesari S;Esau C;Stephens RM;Tannous BA;Krichevsky AM
通讯作者：
Krichevsky AM
影响因子：
14.9
作者：
Ciribilli Y;Monti P;Bisio A;Nguyen HT;Ethayathulla AS;Ramos A;Foggetti G;Menichini P;Menendez D;Resnick MA;Viadiu H;Fronza G;Inga A
通讯作者：
Inga A
影响因子：
11.1
作者：
Biagioni, Francesca;Ben-Moshe, Noa Bossel;Blandino, Giovanni
通讯作者：
Blandino, Giovanni