Lei Chen1, Hongwen Cao1, Yigeng Feng2. 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. 2. Surgical Department I (Urology Department), Shanghai University of Traditional Chinese Medicine Affiliated LONGHUA Hospital, No. 725 Wanping Road South, Xuhui District, Shanghai, 200032, China. fengyigenglh@sohu.com.
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.
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 humanprostate 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 tumorPTX sensitivity. CONCLUSIONS: The downregulation of miR-199a contributes to PTX resistance in prostate cancer. YES1 mediates the regulation of miR-199a in prostate cancerPTX resistance. This miR-199a replacement therapy has potential to overcome PTX resistance.
Entities:
Keywords:
Drug resistance; MiR-199a; Paclitaxel; Prostate cancer; YES1
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