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MiR-199a suppresses prostate cancer paclitaxel resistance by targeting YES1

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Abstract

Purpose

Prostate cancer chemoresistance is a major contributor to the poor survival of patients. MicroRNAs (miRNAs) play an important role in regulating cancer resistance. Here we aim to explore the role and mechanism of miR-199a in regulating prostate cancer resistance.

Methods

MiR-199a expressions in human prostate cancer tissues and cell lines were investigated with real-time PCR (RT-PCR). MiR-199a was ectopically overexpressed in PC3 cells, and resistance to paclitaxel (PTX) was evaluated consequently. The interaction between miR-199a and the oncogene Yamaguchi sarcoma viral homolog 1 (YES1) was assessed after miR-199a overexpression. YES1 was ectopically overexpressed, followed by evaluation of PTX resistance. The efficacy of miR-199a as a therapeutic agent was also investigated in vivo.

Results

Downregulation of miR-199a was characteristic of prostate cancer, particularly recurrent cancers. MiR-199a was suppressed in PTX-resistant cell line. Overexpression of miR-199a inhibited PTX resistance. YES1 was a target of miR-199a, and overexpression of YES1 reversed the effect of miR-199a in suppressing PTX resistance. In vivo, miR-199a increased tumor PTX sensitivity.

Conclusions

The downregulation of miR-199a contributes to PTX resistance in prostate cancer. YES1 mediates the regulation of miR-199a in prostate cancer PTX resistance. This miR-199a replacement therapy has potential to overcome PTX resistance.

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Author information

Author notes

  1. Lei Chen and Hongwen Cao have contributed equally.

Authors and Affiliations

  1. Surgical Department I (Urology Department), Shanghai University of Traditional Chinese Medicine Affiliated LONGHUA Hospital, No. 725 Wanping Road South, Xuhui District, Shanghai, 200032, China

    Lei Chen, Hongwen Cao & Yigeng Feng

Authors
  1. Lei Chen
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  2. Hongwen Cao
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  3. Yigeng Feng
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Contributions

LC and HC contributed to data collection and manuscript writing. YF helped in project development and manuscript writing

Corresponding author

Correspondence to Yigeng Feng.

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Funding

This study was supported by The Third Batch of young Chinese Name Training Program of LongHua Hospital Shanghai University of Traditional Chinese Medicine (Chen Lei). Subject number: RC-2017-01-14; Shanghai Municipal Health and Family Planning Commission Special Subject of Chinese Medicine Research: Inhibitory Effect of Indirubin on Proliferation and Induction of Apoptosis in Prostate Cancer DU145 cells. Subject number: 2016JP014.

Conflict of interest

None of the authors declare competing financial interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All applicable international, national and/or institutional guidelines for the care and use of animals were followed.

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Cite this article

Chen, L., Cao, H. & Feng, Y. MiR-199a suppresses prostate cancer paclitaxel resistance by targeting YES1. World J Urol 36, 357–365 (2018). https://doi.org/10.1007/s00345-017-2143-0

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  • DOI: https://doi.org/10.1007/s00345-017-2143-0

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