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

Publication Type:

Journal Article

Source:

Cancer research, Volume 74, Issue 12, p.3218-27 (2014)

Keywords:

2014, Center-Authored Paper, Genomics Core Facility, Human Biology Division, May 2014, Scientific Imaging Core Facility

Abstract:

The tumor suppressor p53 and microRNAs (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 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. Further, 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'UTR 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.