MicroRNA-125b is a novel negative regulator of p53.

By M. Le, C. Teh, Ng Shyh‐Chang, Huangming Xie, Beiyan Zhou, V. Korzh, H. Lodish, Bing Lim. Genes & Development, 2009

690 citations recorded by the source corpus.

The p53 transcription factor is a key tumor suppressor and a central regulator of the stress response. To ensure a robust and precise response to cellular signals, p53 gene expression must be tightly regulated from the transcriptional to the post-translational levels. Computational predictions suggest that several microRNAs are involved in the post-transcriptional regulation of p53. Here we demonstrate that miR-125b, a brain-enriched microRNA, is a bona fide negative regulator of p53 in both zebrafish and humans. miR-125b-mediated down-regulation of p53 is strictly dependent on the binding of miR-125b to a microRNA response element in the 3' untranslated region of p53 mRNA. Overexpression of miR-125b represses the endogenous level of p53 protein and suppresses apoptosis in human neuroblastoma cells and human lung fibroblast cells. In contrast, knockdown of miR-125b elevates the level of p53 protein and induces apoptosis in human lung fibroblasts and in the zebrafish brain. This phenotype can be rescued significantly by either an ablation of endogenous p53 function or ectopic expression of miR-125b in zebrafish. Interestingly, miR-125b is down-regulated when zebrafish embryos are treated with gamma-irradiation or camptothecin, corresponding to the rapid increase in p53 protein in response to DNA damage. Ectopic expression of miR-125b suppresses the increase of p53 and stress-induced apoptosis. Together, our study demonstrates that miR-125b is an important negative regulator of p53 and p53-induced apoptosis during development and during the stress response.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/36f65af9030aecf7d6c22730894558cded0f2fcb

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Citations in the corpus

MicroRNA control of signal transduction (2010, background): “The miRNA miR-125b is essential to complete p53 repression by targeting it, and loss of miR-125b causes p53-dependent apoptosi”
MicroRNA and cancer (2012, background): “The first report showed that miR-125b mediated downregulation of the p53 protein level suppressed apoptosis in human neuroblastoma cells and human lung fibroblast cells (Le et al., 2009).”
MicroRNA Functions in Stress Responses (2010, positive): “For example, the decay of host miR-27 is triggered by herpesvirus infection (Cazalla et al., 2010), the turnover of miR-183/96/182 clusters, miR-204 and miR-201 is accelerated in dark-adapted retina (Krol et al., 2010), and the level of miR-125b decreases upon DNA damage (Le et al., 2009).”
MicroRNAs in body fluids—the mix of hormones and biomarkers (2011, positive): “On the other hand, miR-125b inhibited apoptosis in neuroblastoma cells in a p53-dependent manne”