Cited by 2,010MicroRNA in disease regulationCancer-related Molecular PathwaysCancer-related molecular mechanisms research

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Transactivation of miR-34a by p53 Broadly Influences Gene Expression and Promotes Apoptosis

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Chang, Tsung-Cheng, Wentzel, Erik A., Kent, Oliver A., Ramachandran, Kalyani, Mullendore, Michael, Lee, Kwang Hyuck, Feldmann, Georg, Yamakuchi, Munekazu, Ferlito, Marcella, Lowenstein, Charles J., Arking, Dan E., Beer, Michael A., Maitra, Anirban, Mendell, Joshua T.·2007·Molecular Cell

DOI 10.1016/j.molcel.2007.05.010PMC PMC1939978

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Abstract

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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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: Chang, Tsung-Cheng
Kent, Oliver A.
Ramachandran, Kalyani
Lee, Kwang Hyuck
Feldmann, Georg
Yamakuchi, Munekazu
Lowenstein, Charles J.
Arking, Dan E.
Beer, Michael A.
Maitra, Anirban
Mendell, Joshua T.
Venue: Molecular Cell
Publisher: Elsevier BV
Published: 2007-06
Volume: 26
Issue: 5
Pages: 745-752
ISSN: 1097-2765 (ISSN-L)
DOI: 10.1016/j.molcel.2007.05.010
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2274 d)
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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Transactivation of miR-34a by p53 Broadly Influences Gene Expression and Promotes Apoptosis

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