Programmed Cell Death 4 (PDCD4) Is an Important Functional Target of the MicroRNA miR-21 in Breast Cancer Cells

Frankel, Lisa B.; Christoffersen, Nanna R.; Jacobsen, Anders; Lindow, Morten; Krogh, Anders; Lund, Anders H.

doi:10.1074/jbc.m707224200

Cited by 1,141MicroRNA in disease regulationCancer-related molecular mechanisms researchCancer-related Molecular Pathways

Programmed Cell Death 4 (PDCD4) Is an Important Functional Target of the MicroRNA miR-21 in Breast Cancer Cells

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Frankel, Lisa B., Christoffersen, Nanna R., Jacobsen, Anders, Lindow, Morten, Krogh, Anders, Lund, Anders H.·2008·Journal of Biological Chemistry

DOI 10.1074/jbc.m707224200

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Abstract

MicroRNAs are emerging as important regulators of cancer-related processes. The miR-21 microRNA is overexpressed in a wide variety of cancers and has been causally linked to cellular proliferation, apoptosis, and migration. Inhibition of mir-21 in MCF-7 breast cancer cells causes reduced cell growth. Using array expression analysis of MCF-7 cells depleted of miR-21, we have identified mRNA targets of mir-21 and have shown a link between miR-21 and the p53 tumor suppressor protein. We furthermore found that the tumor suppressor protein Programmed Cell Death 4 (PDCD4) is regulated by miR-21 and demonstrated that PDCD4 is a functionally important target for miR-21 in breast cancer cells.

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Several mRNAs regulated by miR-21 and anti-miR-21 in glioma cells, including PDCD4, APAF1, FAM3C, SESN1, and GLCCI1, were also identified in an mRNA expression analysis of miR-21 knocked-down MCF7 breast carcinoma cells.
“Several mRNAs regulated by miR-21 and anti-miR-21 in glioma cells (Fig. 3; also see Table S1 in the supplemental material) have recently been identified in an mRNA expression analysis of miR-21 knocked-down MCF7 breast carcinoma cells (14).”
From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [14]
miR-21 is upregulated in most solid tumors, including breast, colorectal and glioma.
“It is upregulated in most solid tumors, including breast, colo-rectal and glioma [5, 10, 12].”
From MicroRNA‐21 protects neurons from ischemic death (2010) · cites this paper as [10]
miR-21 has been shown to be a strong antiapoptotic factor.
“In particular, miRNA-21 (miR-21) has been shown to be a strong antiapoptotic factor [5, 9–11].”
From MicroRNA‐21 protects neurons from ischemic death (2010) · cites this paper as [10]
APAF1, BMPR2, PDCD4, and p21 are up-regulated in MCF-7 breast cancer cells with LNA-miR-21 treatment.
“A subset of the derepressed transcripts, APAF1, BMPR2, PDCD4, and p21 were reported to be up-regulated in MCF-7 breast cancer cells with LNA-miR-21 treatment (15).”
From MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells (2008) · cites this paper as [15]
Three miR-21 targets have been described: PTEN, PDCD4, and TPM1.
“Three miR-21 targets have, thus far, been described: phosphatase and tensin homologue (PTEN), programmed cell death 4 (PDCD4) and Tropomyosin 1 (TPM1; refs.10,[14][15][16].”
From MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells (2008) · cites this paper as [15]

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Authors: Frankel, L. B., Christoffersen, N. R., Jacobsen, A., Lindow, M., Krogh, A., & Lund, A. H.
Affiliations: University of Copenhagen (DK)
Corresponding author: Lund, Anders H.
ORCID: Frankel, Lisa B.
Krogh, Anders
Lund, Anders H.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2008-01
Volume: 283
Issue: 2
Pages: 1026-1033
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m707224200
OpenAlex: W2069104846
Cited by: 1,141
References: 9
Citations by year: 2026: 14 · 2025: 20 · 2024: 18 · 2023: 31 · 2022: 35 · 2021: 39 · 2020: 51 · 2019: 48 · 2018: 51 · 2017: 56 · 2016: 68 · 2015: 92 · 2014: 89 · 2013: 87 · 2012: 88
FWCI: 28.59
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 4658 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
Funders: Rigshospitalet
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords: PDCD4, miR-21, microRNA target regulation, breast cancer, MCF-7 cells, p53, tumor suppressor proteins, cell proliferation, gene expression profiling
MeSH terms: Base Sequence, Breast Neoplasms, Cell Division, Female, Humans, Kinetics, RNA, Neoplasm, RNA-Binding Proteins, Apoptosis, MicroRNAs, Cell Line, Tumor, Apoptosis Regulatory Proteins

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Programmed Cell Death 4 (PDCD4) Is an Important Functional Target of the MicroRNA miR-21 in Breast Cancer Cells

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