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

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149 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 - 2009 Sep 24

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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