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

Cancer research (2014-04-26)
Yemin Wang, Jen-Wei Huang, Maria Castella, David George Huntsman, Toshiyasu Taniguchi
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-MDM2 Antibody, clone 3G9, clone 3G9, from mouse
Sigma-Aldrich
Propidium iodide solution, solution (1.0 mg/ml in water)
Sigma-Aldrich
Propidium iodide, ≥94.0% (HPLC)
Sigma-Aldrich
Propidium iodide, ≥94% (HPLC)