MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer
Abstract
Tumor-suppressor Pdcd4 inhibits transformation and invasion and is downregulated in cancers. So far, it has not been studied as to whether miRNAs, suppressing target expression by binding to the 3'-UTR, regulate Pdcd4 or invasion. The present study was conducted to investigate the regulation of Pdcd4, and invasion/intra-vasation, by miRNAs. A bioinformatics search revealed a conserved target-site for miR-21 within the Pdcd4-3'-UTR at 228-249 nt. In 10 colorectal cell lines, an inverse correlation of miR-21 and Pdcd4-protein was observed. Transfection of Colo206f-cells with miR-21 significantly suppressed a luciferase-reporter containing the Pdcd4-3'-UTR, whereas transfection of RKO with anti-miR-21 increased activity of this construct. This was abolished when a construct mutated at the miR-21/nt228-249 target site was used instead. Anti-miR-21-transfected RKO cells showed an increase of Pdcd4-protein and reduced invasion. Moreover, these cells showed reduced intra-vasation and lung metastasis in a chicken-embryo-metastasis assay. In contrast, overexpression of miR-21 in Colo206f significantly reduced Pdcd4-protein amounts and increased invasion, while Pdcd4-mRNA was unaltered. Resected normal/tumor tissues of 22 colorectal cancer patients demonstrated an inverse correlation between miR-21 and Pdcd4-protein. This is the first study to show that Pdcd4 is negatively regulated by miR-21. Furthermore, it is the first report to demonstrate that miR-21 induces invasion/intravasation…
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miR-21 has been implicated in cellular proliferation, apoptosis, and migration in carcinogenesis.
“This microRNA has been implicated in various aspects of carcinogenesis, including cellular proliferation, apoptosis, and migration.”
From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [1]
Elevated miR-21 expression has been causally linked to proliferation, apoptosis, and migration of several cancer cell lines.
“Elevated miR-21 expression has been causally linked to proliferation, apoptosis, and migration of several cancer cell lines (1, 5, 44, 60).”
From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [1]
PDCD4 protein synthesis is inhibited by microRNAs including miR21.
“The PDCD4 protein synthesis is inhibited by microRNAs including miR21.”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [56]
miR21 targets PDCD4 mRNA and post-transcriptionally down-regulates PDCD4 expression, resulting in increased transformation, invasion, and metastasis of cancer cells.
“These results indicate that the miR21 targets PDCD4 mRNA and post-transcriptionally down-regulates PDCD4 expression, resulting in the increased transformation, invasion, and metastasis of cancer cells [56],”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [56]
Translation of PDCD4 mRNA is inhibited by many kinds of miRNAs including miR21.
“The translation of PDCD4 mRNA is inhibited by many kinds of miRNAs including miR21.”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [56]
The miR21 target site is located at nt233-349 of the PDCD4 3′-UTR region.
“The miR21 target site is located at nt233-349 of PDCD4 3′-UTR region.”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [56]
The effects of miR-21 knockout on osteoclasts seem to result from interaction of miR-21 with PDCD4.
“The effects seem to result from interaction of miR-21 with programmed cell death 4 (PDCD4) [261].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [261]
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 [14]
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- Authors
- Asangani, I. A., Rasheed, S. A. K., Nikolova, D. A., Leupold, J. H., Colburn, N. H., Post, S., & Allgayer, H.
- Affiliations
- Heidelberg University (DE)
- German Cancer Research Center (DE)
- National Institutes of Health (US)
- Corresponding author
- Allgayer, H
- Venue
- Oncogene
- Published
- 2007-10-29
- Volume
- 27
- Issue
- 15
- Pages
- 2128-2136
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2050079849
- Semantic Scholar
- 8d37d0c762402578a795f6ede4693af0ef388eb0
- Cited by
- 1,882
- References
- 40
- Citations by year
- 2026: 30 · 2025: 48 · 2024: 40 · 2023: 62 · 2022: 53 · 2021: 71 · 2020: 87 · 2019: 100 · 2018: 103 · 2017: 116 · 2016: 133 · 2015: 142 · 2014: 169 · 2013: 146 · 2012: 135
- FWCI
- 34.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsches Krebsforschungszentrum
- Alfried Krupp von Bohlen und Halbach-Stiftung
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- miR-21, PDCD4, colorectal cancer, tumor suppressor, microRNA regulation, 3' UTR target sites, post-transcriptional regulation, tumor invasion, intravasation, lung metastasis
- MeSH terms
- Adenocarcinoma, Animals, Base Sequence, Chick Embryo, Humans, Molecular Sequence Data, Neoplasm Invasiveness, Neoplasm Metastasis, Sequence Homology, Nucleic Acid, Tumor Cells, Cultured, Colorectal Neoplasms, Down-Regulation, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, RNA-Binding Proteins, Caco-2 Cells, HT29 Cells, RNA Interference, MicroRNAs, HCT116 Cells, Apoptosis Regulatory Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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