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P53 is positively regulated by miR-542-3p.

ABSTRACT: The tumor suppressor p53 and miRNAs are linked through a complex network. Several miRNAs modulate p53 expression, while p53 regulates the transcription and/or biogenesis of several other miRNAs. Here, we report the development of a cell-based assay used with a library of human miRNA mimics in a high-throughput screen for miRNAs that modulate p53 expression. Overexpression of miRNA (miR)-542-3p in cancer cells elevated p53 expression, stimulated the expression of p53 targets, and inhibited cell proliferation. Mechanistically, miR-542-3p increased p53 protein stability by weakening interactions between p53 and its negative regulator MDM2. Furthermore, miR-542-3p suppressed ribosome biogenesis by downregulating a subset of ribosomal proteins such as RPS23, leading to upregulation of RPL11 and stabilization of p53. The 3'untranslated region in the RPS23 transcript contained a miR-542-3p-binding site, suggesting that RPS23 is a direct target of miR-542-3p. Our results define miR-542-3p as an important new positive regulator of p53 with potential applications in cancer treatment.

SUBMITTER: Wang Y

PROVIDER: S-EPMC4058365 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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p53 is positively regulated by miR-542-3p.

Wang Yemin Y Huang Jen-Wei JW Castella Maria M Huntsman David George DG Taniguchi Toshiyasu T

Cancer research 20140424 12

The tumor suppressor p53 and miRNAs are linked through a complex network. Several miRNAs modulate p53 expression, while p53 regulates the transcription and/or biogenesis of several other miRNAs. Here, we report the development of a cell-based assay used with a library of human miRNA mimics in a high-throughput screen for miRNAs that modulate p53 expression. Overexpression of miRNA (miR)-542-3p in cancer cells elevated p53 expression, stimulated the expression of p53 targets, and inhibited cell p ...[more]

PMID: 24762395

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Project description:Osteosarcoma (OS) is the most common pediatric primary bone tumor, with high malignancy rates and a poor prognosis following metastasis. At present, the role of microRNA (miR)?542?3p in OS remains to be elucidated. The purpose of the present study was to investigate the expression level of miR?542?3p in OS, and its potential molecular mechanisms, via a bioinformatics analysis. First, the expression of miR?542?3p in OS based on the continuous variables of the Gene Expression Omnibus database and PubMed was studied. Subsequently, the potential target genes of miR?542?3p were predicted using gene expression profiles and bioinformatics software. On the basis of the Database for Annotation, Visualization and Integrated Discovery, version 6.8, a study of gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway knowledge base was conducted to explore the biological value of miR?542?3p in OS. Finally, the protein?protein interaction (PPI) network was completed using the STRING database. The expression of miR?542?3p in OS was revealed to be significantly higher compared with that in normal tissue. In total, 1,036 target genes of miR?542?3p were obtained. The results of the GO enrichment analysis revealed that the significant terms were 'bone development', 'cell cycle arrest' and 'intracellular signal transduction'. The results of the KEGG analysis revealed the highlighted pathways that were targeted to miR?542?3p, including the sphingolipid signaling pathway (P=3.91x10?5), the phosphoinositide 3?kinase (PI3K)?AKT serine/threonine kinase (AKT) signaling pathway (P=3.17x10?5) and the insulin signaling pathway (P=1.04x10?5). The PPI network revealed eight hub genes: Ubiquitin?60S ribosomal protein L40, Ras?related C3 botulinum toxin substrate, mitogen?activated protein kinase 1, epidermal growth factor receptor, cystic fibrosis transmembrane conductance regulator, PI3K regulatory subunit 1, AKT1, and actin?related protein 2/3 complex subunit 1A, which may be the key target genes of miR?542?3p in OS. Taken together, these results have demonstrated that miR?542?3p was overexpressed in OS. The potential target genes and biological functions of miR?542?3p may provide novel insights into the differentially expressed genes that are involved in OS.

Dataset Information

P53 is positively regulated by miR-542-3p.

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p53 is positively regulated by miR-542-3p.

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