MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene

Z. Lu, M. Liu, V. Stribinskis, C. M. Klinge, Kenneth Ramos, N. H. Colburn, Y. Li

Research output: Contribution to journalArticle

550 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively control expression of target genes in animals and plants. The microRNA-21 gene (mir-21) has been identified as the only miRNA commonly overexpressed in solid tumors of the lung, breast, stomach, prostate, colon, brain, head and neck, esophagus and pancreas. We initiated a screen to identify miR-21 target genes using a reporter assay and identified a potential miR-21 target in the 3′-UTR of the programmed cell death 4 (PDCD4) gene. We cloned the full-length 3′-UTR of human PDCD4 downstream of a reporter and found that mir-21 downregulated, whereas a modified antisense RNA to miR-21 upregulated reporter activity. Moreover, deletion of the putative miR-21-binding site (miRNA regulatory element, MRE) from the 3′-UTR of PDCD4, or mutations in the MRE abolished the ability of miR-21 to inhibit reporter activity, indicating that this MRE is a critical regulatory region. Western blotting showed that Pdcd4 protein levels were reduced by miR-21 in human and mouse cells, whereas quantitative real-time PCR revealed little difference at the mRNA level, suggesting translational regulation. Finally, overexpression of mir-21 in MCF-7 human breast cancer cells and mouse epidermal JB6 cells promoted soft agar colony formation by downregulating Pdcd4 protein levels. The demonstration that miR-21 promotes cell transformation supports the concept that mir-21 functions as an oncogene by a mechanism that involves translational repression of the tumor suppressor Pdcd4.

Original languageEnglish (US)
Pages (from-to)4373-4379
Number of pages7
JournalOncogene
Volume27
Issue number31
DOIs
StatePublished - Jul 17 2008
Externally publishedYes

Fingerprint

MicroRNAs
Cell Death
Genes
3' Untranslated Regions
Down-Regulation
Breast Neoplasms
Antisense RNA
Small Untranslated RNA
Nucleic Acid Regulatory Sequences
Oncogenes
Esophagus
Agar
Real-Time Polymerase Chain Reaction
Prostate
Pancreas
Stomach
Colon
Proteins
Neck
Western Blotting

Keywords

  • Cell transformation
  • MicroRNA
  • miR-21
  • PDCD4
  • Tumor suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Lu, Z., Liu, M., Stribinskis, V., Klinge, C. M., Ramos, K., Colburn, N. H., & Li, Y. (2008). MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Oncogene, 27(31), 4373-4379. https://doi.org/10.1038/onc.2008.72

MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. / Lu, Z.; Liu, M.; Stribinskis, V.; Klinge, C. M.; Ramos, Kenneth; Colburn, N. H.; Li, Y.

In: Oncogene, Vol. 27, No. 31, 17.07.2008, p. 4373-4379.

Research output: Contribution to journalArticle

Lu, Z, Liu, M, Stribinskis, V, Klinge, CM, Ramos, K, Colburn, NH & Li, Y 2008, 'MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene', Oncogene, vol. 27, no. 31, pp. 4373-4379. https://doi.org/10.1038/onc.2008.72
Lu, Z. ; Liu, M. ; Stribinskis, V. ; Klinge, C. M. ; Ramos, Kenneth ; Colburn, N. H. ; Li, Y. / MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. In: Oncogene. 2008 ; Vol. 27, No. 31. pp. 4373-4379.
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