1. Academic Validation
  2. PKMYT1 is associated with prostate cancer malignancy and may serve as a therapeutic target

PKMYT1 is associated with prostate cancer malignancy and may serve as a therapeutic target

  • Gene. 2020 Jun 20;744:144608. doi: 10.1016/j.gene.2020.144608.
Jianan Wang 1 Lin Wang 1 Saipeng Chen 1 Huahong Peng 1 Longfei Xiao 1 E Du 1 Yan Liu 1 Dong Lin 2 Yuzhuo Wang 2 Yong Xu 3 Kuo Yang 4
Affiliations

Affiliations

  • 1 Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China.
  • 2 Vancouver Prostate Centre, Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC V6H 3Z6, Canada; Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
  • 3 Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China. Electronic address: [email protected].
  • 4 Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China. Electronic address: [email protected].
Abstract

Prostate Cancer (PCa) is the third most common malignancy worldwide. Novel and effective therapeutic targets are needed for PCa. The purpose of this study was to discover novel therapeutic targets for PCa by performing advanced analysis on PCa RNA sequencing (RNAseq) data from The Cancer Genome Atlas (TCGA). Weighted correlation-network analysis (WGCNA) was performed on the RNAseq data of tumor samples, and the module most relevant to the Gleason score was identified. Combining differential gene-expression analysis and survival analysis, we narrowed down potential therapeutic target genes and found that PKMYT1 might be one. Subsequently, functional studies (i.e., cell-proliferation assays, cell cycle analysis, and colony-formation assays) demonstrated that knockdown of PKMYT1 significantly inhibited the growth of PCa cells. Further investigation illustrated that PKMYT1 promoted the growth of PCa cells through targeting CCNB1 and CCNE1 expression. In addition, fostamatinib, an inhibitor of PKMYT1, effectively inhibited the proliferation of PCa cells. Taken together, our results suggest that PKMYT1 is a gene associated with malignancy of PCa and is a novel therapeutic target.

Keywords

Fostamatinib; Gleason score; PKMYT1; Prostate cancer; Weighted correlation-network analysis.

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