Abstract
Recently, the transcription factor encoded by tumor suppressor gene p53 was shown to regulate the expression of microRNAs. The most significant induction by p53 was observed for the microRNAs miR-34a and miR-34b/c, which turned out to be direct p53 target genes. Ectopic miR-34 expression induces apoptosis, cell-cycle arrest or senescence. In many tumor types the promoters of the miR-34a and the miR-34b/c genes are subject to inactivation by CpG methylation. MiR-34a resides on 1p36 and is commonly deleted in neuroblastomas. Furthermore, the loss of miR-34 expression has been linked to resistance against apoptosis induced by p53 activating agents used in chemotherapy. In this review, the evidence for a role of miR-34a and miR-34b/c in the apoptotic response of normal and tumor cells is surveyed.
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Abbreviations
- ATM:
-
ataxia teleangiectasia mutated
- CDK:
-
cyclin-dependent kinase
- CLL:
-
chronic lymphocytic leukemia
- CpG:
-
cytosine–guanosine dinucleotide
- HDAC:
-
histone deacetylase
- LNA:
-
locked nucleic acids
- LOH:
-
loss of heterozygosity
- miRNA:
-
microRNA
- miRNP:
-
miRNA–protein complexes
- NSCLC:
-
non-small cell lung cancer
- siRNA:
-
small interfering RNA
- SIRT1:
-
silent information regulator 1
- UTR:
-
untranslated region of mRNA
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Acknowledgements
The author wishes to thank AK Kretzschmar for help with preparing figure 2 and B Hansen for compiling data for table 1. Work in Heiko Hermeking's lab is supported by the DFG, the Deutsche Krebshilfe and the Rudolf-Bartling-Stiftung.
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