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Transactivation of miR-34a by p53 Broadly Influences Gene Expression and Promotes Apoptosis
Open accessAbstract
The p53 tumor suppressor protein is a critical regulator of the cellular response to cancer-initiating insults such as genotoxic stress. In this report, we demonstrate that microRNAs (miRNAs) are important components of the p53 transcriptional network. Global miRNA expression analyses identified a cohort of miRNAs that exhibit p53-dependent upregulation following DNA damage. One such miRNA, miR-34a, is commonly deleted in human cancers and, as shown here, frequently absent in pancreatic cancer cells. Characterization of the miR-34a primary transcript and promoter demonstrates that this miRNA is directly transactivated by p53. Expression of miR-34a causes dramatic reprogramming of gene expression and promotes apoptosis. Much like the known set of p53-regulated genes, miR-34a-responsive genes are highly enriched for those that regulate cell-cycle progression, apoptosis, DNA repair, and angiogenesis. Therefore, it is likely that an important function of miR-34a is the modulation and fine-tuning of the gene expression program initiated by p53.
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“Considering other proteins significantly changed in AsymAD, like TMPO and HNRNPF (Table S2), the genetic interaction network landscape had edges that were consistently supported by changes found in a microarray study which identified transcripts altered downstream of an age-associated overexpressed circulating and brain-resident microRNA, mIR34-a (Chang et al., 2007; Li et al., 2011).”
From A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer’s Disease (2017) · cites this paper as Chang et al., 2007
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Metadata
- Authors
- Chang, T.-C., Wentzel, E. A., Kent, O. A., Ramachandran, K., Mullendore, M., Lee, K. H., Feldmann, G., Yamakuchi, M., Ferlito, M., Lowenstein, C. J., Arking, D. E., Beer, M. A., Maitra, A., & Mendell, J. T.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Mendell, Joshua T.
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 26
- Issue
- 5
- Pages
- 745-752
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC1939978
- OpenAlex
- W2038167014
- Cited by
- 2,010
- References
- 59
- Citations by year
- 2026: 23 · 2025: 37 · 2024: 34 · 2023: 47 · 2022: 54 · 2021: 94 · 2020: 84 · 2019: 89 · 2018: 94 · 2017: 116 · 2016: 121 · 2015: 133 · 2014: 186 · 2013: 159 · 2012: 177
- FWCI
- 45.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Rita Allen Foundation
- Lustgarten Foundation
- Allen Foundation
- National Cancer Institute (R01CA113669, R01CA120185)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- miR-34a, p53, DNA damage response, apoptosis, gene expression reprogramming, pancreatic cancer, cell cycle regulation, DNA repair, angiogenesis, tumor suppressor
- MeSH terms
- Base Sequence, DNA Damage, Humans, Pancreatic Neoplasms, Promoter Regions, Genetic, RNA, Neoplasm, Transcriptional Activation, Gene Expression, Tumor Suppressor Protein p53, Apoptosis, MicroRNAs, Cell Line, Tumor
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