MiR-199a suppresses prostate cancer paclitaxel resistance by targeting YES1
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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.
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.
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.
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.
KeywordsMiR-199a Paclitaxel Drug resistance Prostate cancer YES1
LC and HC contributed to data collection and manuscript writing. YF helped in project development and manuscript writing
Compliance with ethical standards
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.
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.
- 3.GrÃ¼nwald V, DeGraffenried L, Russel D, Friedrichs WE, Ray RB, Hidalgo M (2002) Inhibitors of mTOR reverse doxorubicin resistance conferred by PTEN status in prostate cancer cells. Can Res 62:6141–6145Google Scholar
- 9.Fornari F, Milazzo M, Chieco P, Negrini M, Calin GA, Grazi GL, Pollutri D, Croce CM, Bolondi L, Gramantieri L (2010) MiR-199a-3p regulates mTOR and c-Met to influence the doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res 70:5184–5193. https://doi.org/10.1158/0008-5472.CAN-10-0145 CrossRefPubMedGoogle Scholar
- 14.Giannakakou P, Sackett DL, Kang YK, Zhan ZR, Buters JTM, Fojo T, Poruchynsky MS (1997) Paclitaxel-resistant human ovarian cancer cells have mutant beta-tubulins that exhibit impaired paclitaxel-driven polymerization. J Biol Chem 272:17118–17125. https://doi.org/10.1074/jbc.272.27.17118 CrossRefPubMedGoogle Scholar
- 15.Chen D, Guo WJ, Qiu ZP, Wang QF, Li Y, Liang LH, Liu L, Huang SL, Zhao YJ, He XH (2015) MicroRNA-30d-5p inhibits tumour cell proliferation and motility by directly targeting CCNE2 in non-small cell lung cancer. Cancer Lett 362:208–217. https://doi.org/10.1016/j.canlet.2015.03.041 CrossRefPubMedGoogle Scholar
- 21.Bouchie A (2013) First microRNA mimic enters clinic. Nat Res 31(7):577Google Scholar