ZEB1 activated-VPS9D1-AS1 promotes the tumorigenesis and progression of prostate cancer by sponging miR-4739 to upregulate MEF2D

Biomed Pharmacother. 2020 Feb:122:109557. doi: 10.1016/j.biopha.2019.109557. Epub 2019 Dec 30.

Abstract

Prostate cancer (PCa) is a destructive malignancy with a bad prognosis. LncRNA VPS9D1-AS1 has recently been delineated as an oncogene in some kinds of tumor, whereas, the function of VPS9D1-AS1 in PCa remains to be clarified. In this study, we researched its underlying role in PCa. The expression of VPS9D1-AS1 was conspicuously upregulated in PCa tissues and cells. And absence of VPS9D1-AS1 inhibited cell proliferation, migration and invasion, and promoted cell apoptosis in PCa. In addition, VPS9D1-AS1 overexpression led to opposite results. Furthermore, VPS9D1-AS1/MEF2D could sponge with miR-4739. VPS9D1-AS1/MEF2D and miR-4739 were inversely correlated in tumor cells. And the expression of miR-4739 is markedly downregulated in PCa, meanwhile, that of MEF2D exhibited the opposite tendency. However, MEF2D was positively regulated by VPS9D1-AS1. Moreover, MEF2D upregulation offset the suppressive effects of VPS9D1-AS1 deficiency on cell proliferation, migration and invasion in PCa. Additionally, ZEB1 contained the binding sites of VPS9D1-AS1 promoter, and there existed positive relation between them. Taken together, above results illustrated that ZEB1 activated-VPS9D1-AS1 promotes the tumorigenesis and progression of PCa by sponging miR-4739 to upregulate MEF2D, which offering a new useful reference for studying the development process of PCa.

Keywords: MEF2D; Prostate cancer; VPS9D1-AS1; ZEB1; miR-4739.

MeSH terms

  • Apoptosis
  • Carcinogenesis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MEF2 Transcription Factors / genetics
  • MEF2 Transcription Factors / metabolism
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism*
  • Zinc Finger E-box-Binding Homeobox 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism*

Substances

  • MEF2 Transcription Factors
  • MEF2D protein, human
  • MIRN4739 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • long non-coding RNA VPS9D1-AS1, human