Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Aug 7;17(15):1298-307.
doi: 10.1016/j.cub.2007.06.068. Epub 2007 Jul 26.

p53-mediated activation of miRNA34 candidate tumor-suppressor genes

Guido T Bommer  1 , Isabelle Gerin, Ying Feng, Andrew J Kaczorowski, Rork Kuick, Robert E Love, Yali Zhai, Thomas J Giordano, Zhaohui S Qin, Bethany B Moore, Ormond A MacDougald, Kathleen R Cho, Eric R Fearon
Affiliations
Free article

p53-mediated activation of miRNA34 candidate tumor-suppressor genes

Guido T Bommer et al. Curr Biol. .
Free article

Abstract

Background: In response to varied cell stress signals, the p53 tumor-suppressor protein activates a multitude of genes encoding proteins with functions in cell-cycle control, DNA repair, senescence, and apoptosis. The role of p53 in transcription of other types of RNAs, such as microRNAs (miRNAs) is essentially unknown.

Results: Using gene-expression analyses, reporter gene assays, and chromatin-immunoprecipitation approaches, we present definitive evidence that the abundance of the three-member miRNA34 family is directly regulated by p53 in cell lines and tissues. Using array-based approaches and algorithm predictions, we define genes likely to be directly regulated by miRNA34, with cell-cycle regulatory genes being the most prominent class. In addition, we provide functional evidence, obtained via antisense oligonucleotide transfection and the use of mouse embryonic stem cells with loss of miRNA34a function, that the BCL2 protein is regulated directly by miRNA34. Finally, we demonstrate that the expression of two miRNA34s is dramatically reduced in 6 of 14 (43%) non-small cell lung cancers (NSCLCs) and that the restoration of miRNA34 expression inhibits growth of NSCLC cells.

Conclusions: Taken together, the data suggest the miRNA34s might be key effectors of p53 tumor-suppressor function, and their inactivation might contribute to certain cancers.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

Substances

Associated data

  NODES
INTERN 3
Project 1
twitter 2