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The p53/miR-34 axis in development and disease Free
Matjaz Rokavec1, Huihui Li1, Longchang Jiang1, and Heiko Hermeking1,2,3,*
1Experimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-Universität München, 80337 Munich, Germany
2German Cancer Consortium (DKTK), 69120 Heidelberg, Germany
3German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
*Correspondence to:Heiko Hermeking, E-mail: heiko.hermeking@med.uni-muenchen.de
J Mol Cell Biol, Volume 6, Issue 3, June 2014, Pages 214-230  https://doi.org/10.1093/jmcb/mju003
Keyword: p53, miR-34, miR-34a, miR-34b/c, cancer, metastasis tumor suppression

The tumor suppressor p53 is one of the most frequently mutated genes in human cancers. MicroRNAs (miRNAs) are small non-protein coding RNAs that regulate gene expression on the post-transcriptional level. Recently, it was shown that p53 regulates the expression of several miRNAs, thereby representing an important mechanism of p53 signaling. Several independent studies identified the members of the miR-34 family as the most prevalent p53-induced miRNAs. miR-34s are frequently silenced in variety of tumor entities, suggesting that they are important tumor suppressors. Indeed, ectopic expression of miR-34s inhibits proliferation, epithelial to mesenchymal transition, migration, invasion, and metastasis of various cancer cell entities. Moreover, delivery or re-expression of miR-34 leads to notable repression of tumor growth and metastasis in cancer mouse models, and may therefore represent an efficient strategy for future cancer therapeutics. Besides their crucial functions in cancer, members of the miR-34 family also play important roles in spermatogenesis, stem cell differentiation, neuronal development, aging, and cardiovascular functions. Consequently, miR-34 has also been implicated in various non-cancerous diseases, such as brain disorders, osteoporosis, and cardiovascular complications.