The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition

Toxicol Appl Pharmacol. 2021 Jan 15:411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.


Benign prostatic hyperplasia (BPH) is an age-related disease in men. Mesenchymal /stromal and epithelial cells interactions are essential to prostate functions. In this study, human nonmalignant prostate epithelial RWPE-1 cells were cocultured with testosterone (TE) -exposed prostate stromal fibroblasts WPMY-1 cells (TE-WPMY-1). The survival rate, epithelial-mesenchymal transition (EMT) and collagen deposition of RWPE-1 were observed. The expression profiles of circRNAs, lncRNAs and mRNAs in WPMY-1-derived exosome-like vesicles (WPMY-1-exo) were explored by high-throughput RNA sequencing. Firstly, both TE-WPMY-1 and TE-WPMY-1-exo significantly promoted RWPE-1 cells proliferation. Secondly, 41 circRNAs, 132 lncRNAs and 1057 mRNAs were differentially expressed (DE) between TE-WPMY-1-exo and the control. Functional enrichment analyses, co-expression analyses and quantitative real-time PCR verification showed that the DE RNAs played important roles in cell proliferation, structure, phenotype and fibrosis. Lastly, blocking WPMY-1-exo biogenesis/release by GW4869 can attenuate TE-WPMY-1-stimulated RWPE-1 cells EMT and collagen deposition. Taken together, our results indicated that WPMY-1-exo modulated the phenotypes changes and collagen deposition of prostate epithelial cells. It provided a novel basis for understanding the underlying mechanisms of RWPE-1 cells EMT and fibrosis induced by WPMY-1 in BPH.

Keywords: Benign prostatic hyperplasia; Epithelial cells; Epithelial-mesenchymal transition; Exosome-like vesicles; Stromal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Proliferation*
  • Coculture Techniques
  • Collagen / metabolism
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Epithelial-Mesenchymal Transition*
  • Exosomes / drug effects
  • Exosomes / genetics
  • Exosomes / metabolism*
  • Exosomes / pathology
  • Fibrosis
  • Gene Regulatory Networks
  • Humans
  • Male
  • Paracrine Communication*
  • Phenotype
  • Prostate / drug effects
  • Prostate / metabolism*
  • Prostate / pathology
  • Prostatic Hyperplasia / genetics
  • Prostatic Hyperplasia / metabolism*
  • Prostatic Hyperplasia / pathology
  • RNA, Circular / genetics
  • RNA, Circular / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism*
  • Stromal Cells / pathology
  • Testosterone / pharmacology
  • Transcriptome


  • RNA, Circular
  • RNA, Long Noncoding
  • RNA, Messenger
  • Testosterone
  • Collagen