Long noncoding RNA PVT1 promotes EMT via mediating microRNA-186 targeting of Twist1 in prostate cancer

Gene. 2018 May 15;654:36-42. doi: 10.1016/j.gene.2018.02.036. Epub 2018 Feb 13.

Abstract

The pathogenesis and the underlying mechanism of endothelial-mesenchymal transition in prostate cancer remain unclear. Plasmacytoma variant translocation 1 (PVT1), a novel long non-coding RNA maps to 8q24.21, and in many tumor studies the up-regulation of PVT1 has already been reported. PVT1 is closely related to tumor cell proliferation, invasion, and metastasis. In this study, we employed a combination of techniques to study the role of PVT1 in prostate cancer, which included bioinformatic analysis, Western blotting and cell migration assays of prostate cancer cell lines. We report that PVT1 promotes prostate cancer invasion and metastasis by modulating EMT. Furthermore, PVT1 can promote EMT by up-regulation of Twist1, a transcription factor associated with EMT. We then confirmed that PVT1 acts as a sponge for miRNA-186-5p and positively regulates Twist1 by a sponge effect. Therefore, this study has revealed a novel MECHANISM for the promotion of EMT in prostate cancer by PVT1. Our findings suggest that the PVT1/miR-186/Twist1 regulatory axis may be a new therapeutic target for prostate cancer.

Keywords: EMT; PVT1; Prostate cancer; Survival outcomes; Twist; lncRNA.

MeSH terms

  • Aged
  • Binding Sites
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Computational Biology
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Nuclear Proteins / metabolism*
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / metabolism*
  • RNA, Long Noncoding / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Sequence Analysis, RNA
  • Twist-Related Protein 1 / metabolism*
  • Up-Regulation

Substances

  • MIRN186 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • PVT1 long-non-coding RNA, human
  • RNA, Long Noncoding
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • Prostate-Specific Antigen