The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
p53 represses c-Myc through induction of the tumor suppressor miR-145
Open accessAbstract
The tumor suppressor p53 negatively regulates a number of genes, including the proto-oncogene c-Myc, in addition to activating many other genes. One mechanism of the p53-mediated c-Myc repression may involve transcriptional regulation. However, it is not clear whether microRNAs (miRNAs) play a role in the p53-mediated posttranscriptional regulation of c-Myc. In this study, we show that a putative tumor suppressor, miR-145 , is expressed through the phosphoinositide-3 kinase (PI-3K)/Akt and p53 pathways. Importantly, p53 transcriptionally induces the expression of miR-145 by interacting with a potential p53 response element (p53RE) in the miR-145 promoter. We further show that c-Myc is a direct target for miR-145 . Although miR-145 silences the expression of c-Myc, anti- miR-145 enhances its expression. This specific silencing of c-Myc by miR-145 accounts at least in part for the miR-145 -mediated inhibition of tumor cell growth both in vitro and in vivo. Finally, the blockade of miR-145 by anti- miR-145 is able to reverse the p53-mediated c-Myc repression. Together, these results define the role of miR-145 in the posttranscriptional regulation of c-Myc by p53 and suggest that, as a new member of the p53 regulatory network, miR-145 provides a direct link between p53 and c-Myc in this gene regulatory network.
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Cites
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A Global Map of p53 Transcription-Factor Binding Sites in the Human Genome
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“Moreover, c-Myc can enhance p53 expression through p19Arf (31).”
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“degradation, inactivation (dephosphorylation) of Akt increases the stability of p53 (16).”
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Metadata
- Authors
- Sachdeva, M., Zhu, S., Wu, F., Wu, H., Walia, V., Kumar, S., Elble, R., Watabe, K., & Mo, Y.-Y.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-03-03
- Volume
- 106
- Issue
- 9
- Pages
- 3207-3212
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2099692224
- Cited by
- 841
- References
- 4
- FWCI
- 21.17
- Type
- journal article
- Language
- en
- Open access
- green
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- Sachdeva, M., Zhu, S., Wu, F., Wu, H., Walia, V., Kumar, S., Elble, R., Watabe, K., & Mo, Y.-Y. (2009). p53 represses c-Myc through induction of the tumor suppressor miR-145. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0808042106
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