MicroRNA-330 acts as tumor suppressor and induces apoptosis of prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation

K. H. Lee, Y. L. Chen, S. D. Yeh, M. Hsiao, J. T. Lin, Y. G. Goan, P. J. Lu

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) make up a novel class of gene regulators; they function as oncogenes or tumor suppressors by targeting tumor-suppressor genes or oncogenes. A recent study that analysed a large number of human cancer cell lines showed that miR-330 is a potential tumor-suppressor gene. However, the function and molecular mechanism of miR-330 in determining the aggressiveness of human prostate cancer has not been studied. Here, we show that miR-330 is significantly lower expressed in human prostate cancer cell lines than in nontumorigenic prostate epithelial cells. Bioinformatics analyses reveal a conserved target site for miR-330 in the 3′-untranslated region (UTR) of E2F1 at nucleotides 1018-1024. MiR-330 significantly suppressed the activity of a luciferase reporter containing the E2F1-3′-UTR in the cells. This activity could be abolished with the transfection of anti-miR-330 or mutated E2F1-3′-UTR. In addition, the expression level of miR-330 and E2F1 was inversely correlated in cell lines and prostate cancer specimens. After overexpressing of miR-330 in PC-3 cells, cell growth was suppressed by reducing E2F1-mediated Akt phosphorylation and thereby inducing apoptosis. Collectively, this is the first study to show that E2F1 is negatively regulated by miR-330 and also show that miR-330 induces apoptosis in prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation.

Original languageEnglish
Pages (from-to)3360-3370
Number of pages11
JournalOncogene
Volume28
Issue number38
DOIs
Publication statusPublished - Sep 24 2009

Fingerprint

MicroRNAs
Prostatic Neoplasms
3' Untranslated Regions
Phosphorylation
Apoptosis
Tumor Suppressor Genes
Oncogenes
Cell Line
Neoplasms
Regulator Genes
Computational Biology
Luciferases
Transfection
Prostate
Nucleotides
Epithelial Cells
Growth

Keywords

  • Akt
  • Apoptosis
  • E2F1
  • MiR-330
  • Prostate cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

MicroRNA-330 acts as tumor suppressor and induces apoptosis of prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation. / Lee, K. H.; Chen, Y. L.; Yeh, S. D.; Hsiao, M.; Lin, J. T.; Goan, Y. G.; Lu, P. J.

In: Oncogene, Vol. 28, No. 38, 24.09.2009, p. 3360-3370.

Research output: Contribution to journalArticle

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