Downregulation of miR-221, -30d, and -15a contributes to pathogenesis of prostate cancer by targeting Bmi-1
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Prostate cancer is the second leading cause of cancer-related deaths of men. Bmi-1, a member of PcG family of proteins, has been implicated in the pathogenesis of prostate cancer, and disturbed profile of microRNAs (miRNAs) has been found in prostate cancer tissues. How Bmi-1 is regulated by miRNAs is unclear. In this study, we screened 18 miRNAs that potentially repress the expression of Bmi-1 using a dual luciferase system and found that 12 miRNAs could bind with the 3′-untranslated region of Bmi-1 mRNA. Using qRT-PCR, we found that expression of miR-221, -15a, and -30d was significantly reduced in prostate cancer tissues. Subsequent functional study indicated that miR-221 and miR-30d can repress prostate cancer cell proliferation, and this effect can be partially rescued by Bmi-1 overexpression. Our study constructs the relation between downregulated miR-221 and miR-30d and prostate cancer pathogenesis. These results indicate that miR-221 and miR-30d are candidate tumor suppressor miRNAs in prostate cancer and therefore serve as potential clinical classification markers and therapeutic targets for human prostate cancer.
Key wordsmiRNA prostate cancer Bmi-1 cell proliferation
Argonaute RISC catalytic component 2
B-cell specific Moloney leukemia virus insertion region homolog 1 (oncoprotein from PcG (polycomb group))
small interfering RNA
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- 2.Kang, M. K., Kim, R. H., Kim, S. J., Yip, F. K., Shin, K. H., Dimri, G. P., Christensen, R., Han, T., and Park, N. H. (2007) Elevated Bmi-1 expression is associated with dysplastic cell transformation during oral carcinogenesis and is required for cancer cell replication and survival, Brit. J. Cancer, 96, 126–133.CrossRefPubMedCentralPubMedGoogle Scholar
- 4.Ammirante, M., Kuraishy, A. I., Shalapour, S., Strasner, A., Ramirez-Sanchez, C., Zhang, W., Shabaik, A., and Karin, M. (2013) An IKKalpha-E2F1-BMI1 cascade activated by infiltrating B cells controls prostate regeneration and tumor recurrence, Genes Devel., 27, 1435–1440.CrossRefPubMedCentralPubMedGoogle Scholar