Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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FAM46B inhibits cell proliferation and cell cycle progression in prostate cancer through ubiquitination of β-catenin

  • Liang, Tao (Department of Urology, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences) ;
  • Ye, Xuxiao (Department of Urology, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences) ;
  • Liu, Yuanyuan (Department of Urology, Affiliated Hospital of Binzhou Medical University) ;
  • Qiu, Xinkai (Department of Urology, Affiliated Hospital of Binzhou Medical University) ;
  • Li, Zuowei (Department of Urology, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences) ;
  • Tian, Binqiang (Department of Urology, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences) ;
  • Yan, Dongliang (Department of Urology, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences)
  • Received : 2018.04.23
  • Accepted : 2018.08.06
  • Published : 2018.12.30
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Abstract

FAM46B is a member of the family with sequence similarity 46. Little is known about the expression and functional role (s) of FAM46B in prostate cancer (PC). In this study, the expression of FAM46B expression in The Cancer Genome Atlas, GSE55945, and an independent hospital database was measured by bioinformatics and real-time PCR analysis. After PC cells were transfected with siRNA or a recombinant vector in the absence or presence of a ${\beta}$-catenin signaling inhibitor (XAV-939), the expression levels of FAM46B, C-myc, Cyclin D1, and ${\beta}$-catenin were measured by western blot and realtime PCR. Cell cycle progression and cell proliferation were measured by flow cytometry and the CCK-8 assay. The effects of FAM46B on tumor growth and protein expression in nude mice with PC tumor xenografts were also measured. Our results showed that FAM46B was downregulated but that ${\beta}$-catenin was upregulated in patients with PC. FAM46B silencing promoted cell proliferation and cell cycle progression in PC, which were abrogated by XAV-939. Moreover, FAM46B overexpression inhibited PC cell cycle progression and cell proliferation in vitro and tumor growth in vivo. FAM46B silencing promoted ${\beta}$-catenin protein expression through the inhibition of ${\beta}$-catenin ubiquitination. Our data clearly show that FAM46B inhibits cell proliferation and cell cycle progression in PC through ubiquitination of ${\beta}$-catenin.

Keywords

Acknowledgement

Supported by : Pudong New Area Science and Technology Development Fund

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