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Downregulation of miR-221, -30d, and -15a contributes to pathogenesis of prostate cancer by targeting Bmi-1

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Abstract

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.

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Abbreviations

AGO2:

Argonaute RISC catalytic component 2

Bmi-1:

B-cell specific Moloney leukemia virus insertion region homolog 1 (oncoprotein from PcG (polycomb group))

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

miRNA:

microRNA

PCa:

prostate cancer

siRNA:

small interfering RNA

3′-UTR:

3′-untranslated region

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Authors and Affiliations

  1. Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1630 Dong Fang Road, Shanghai, 2000127, China

    Hanqing Xuan, Wei Xue, Jiahua Pan, Jianjun Sha, Baijun Dong & Yiran Huang

Authors
  1. Hanqing Xuan
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  2. Wei Xue
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  3. Jiahua Pan
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  4. Jianjun Sha
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  5. Baijun Dong
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  6. Yiran Huang
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Corresponding author

Correspondence to Wei Xue.

Additional information

Published in Russian in Biokhimiya, 2015, Vol. 80, No. 3, pp. 339–347.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM14-144, January 25, 2015.

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Xuan, H., Xue, W., Pan, J. et al. Downregulation of miR-221, -30d, and -15a contributes to pathogenesis of prostate cancer by targeting Bmi-1. Biochemistry Moscow 80, 276–283 (2015). https://doi.org/10.1134/S0006297915030037

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  • DOI: https://doi.org/10.1134/S0006297915030037

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