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

Oncogene volume 28, pages 3360–3370 (2009)Cite this article

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.

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Acknowledgements

We thank the grant support from National Cheng Kung University Hospital Grant (NCKUH-9701004 to P-J Lu), National Science Council (NSC 97-2311-B-006-003-MY3 to P-J Lu and NSC-98-3112-B-006-012 to Y-L Chen). We also thank Dr Chen in the Department Urology College of Pharmacy and Comprehensive Cancer Center, The Ohio State University, for his generous gifts of Akt plasmid DNA.

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Authors and Affiliations

  1. Institute of Basic Medical Sciences, National Cheng Kung University, College of Medicine, Tainan, Taiwan

    K-H Lee

  2. Institute of Oral Medicine, National Cheng Kung University, College of Medicine, Tainan, Taiwan

    Y-L Chen

  3. Department of Urology, Taipei Medical University, Taipei, Taiwan

    S-D Yeh

  4. Genomics Research Center, Academia Sinica, Taipei, Taiwan

    M Hsiao

  5. Division of Urology Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

    J-T Lin

  6. Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

    Y-G Goan

  7. Department of Surgery, National Yang-Ming University, Taipei, Taiwan

    Y-G Goan

  8. Institute of Clinical Medicine, National Cheng Kung University, College of Medicine, Tainan, Taiwan

    P-J Lu

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  1. K-H Lee
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Correspondence to P-J Lu.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Lee, KH., Chen, YL., Yeh, SD. et al. MicroRNA-330 acts as tumor suppressor and induces apoptosis of prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation. Oncogene 28, 3360–3370 (2009). https://doi.org/10.1038/onc.2009.192

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