Cited by 1,882MicroRNA in disease regulationCancer-related molecular mechanisms researchMechanisms of cancer metastasis

MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer

Asangani, I A, Rasheed, S A K, Nikolova, D A, Leupold, J H, Colburn, N H, Post, S, Allgayer, H·2008·Oncogene

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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Crossref · 10.1038/sj.onc.1210856

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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.”
  • 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).”
  • PDCD4 protein synthesis is inhibited by microRNAs including miR21.

    “The PDCD4 protein synthesis is inhibited by microRNAs including miR21.”
  • 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],”
  • 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.”

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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
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

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