The p53/miR-34 axis in development and disease
Open Access
- 9 May 2014
- journal article
- review article
- Published by Oxford University Press (OUP) in Journal of Molecular Cell Biology
- Vol. 6 (3), 214-230
- https://doi.org/10.1093/jmcb/mju003
Abstract
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.Keywords
This publication has 100 references indexed in Scilit:
- MIR‐34c regulates mouse embryonic stem cells differentiation into male germ‐like cells through RARgCell Biochemistry and Function, 2012
- Tumor Suppression in the Absence of p53-Mediated Cell-Cycle Arrest, Apoptosis, and SenescenceCell, 2012
- MiR-34 modulates Caenorhabditis elegans lifespan via repressing the autophagy gene atg9AGE, 2011
- Identification of the receptor tyrosine kinase AXL in breast cancer as a target for the human miR-34a microRNABreast Cancer Research and Treatment, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- MicroRNA-34a regulation of endothelial senescenceBiochemical and Biophysical Research Communications, 2010
- MicroRNA-34a Perturbs B Lymphocyte Development by Repressing the Forkhead Box Transcription Factor Foxp1Immunity, 2010
- Nonalcoholic steatohepatitis is associated with altered hepatic MicroRNA expressionHepatology, 2008
- The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem CellsCell, 2008
- Impact of mutant p53 functional properties onTP53mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 databaseHuman Mutation, 2007