Cell-type specific expression of oncogenic and tumor suppressive microRNAs in the human prostate and prostate cancer. Academic Article uri icon

Overview

abstract

  • MiR-1 and miR-143 are frequently reduced in human prostate cancer (PCa), while miR-141 and miR-21 are frequently elevated. Consequently, these miRNAs have been studied as cell-autonomous tumor suppressors and oncogenes. However, the cell-type specificity of these miRNAs is not well defined in prostate tissue. Through two different microdissection techniques, and droplet digital RT-PCR, we quantified these miRNAs in the stroma and epithelium of radical prostatectomy specimens. In contrast to their purported roles as cell-autonomous tumor suppressors, we found miR-1 and miR-143 expression to be predominantly stromal. Conversely, miR-141 was predominantly epithelial. miR-21 was detected in both stroma and epithelium. Strikingly, the levels of miR-1 and miR-143 were significantly reduced in tumor-associated stroma, but not tumor epithelium. Gene expression analyses in human cell lines, tissues, and prostate-derived stromal cultures support the cell-type selective expression of miR-1, miR-141, and miR-143. Analyses of the PCa Genome Atlas (TCGA-PRAD) showed a strong positive correlation between stromal markers and miR-1 and miR-143, and a strong negative correlation between stromal markers and miR-141. In these tumors, loss of miR-1 and gain of miR-21 was highly associated with biochemical recurrence. These data shed new light on stromal and epithelial miRNA expression in the PCa tumor microenvironment.

publication date

  • May 8, 2018

Research

keywords

  • Gene Expression Regulation, Neoplastic
  • MicroRNAs
  • Neoplasm Recurrence, Local
  • Prostatic Neoplasms

Identity

PubMed Central ID

  • PMC5940660

Scopus Document Identifier

  • 85046873963

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0051862

PubMed ID

  • 29739972

Additional Document Info

volume

  • 8

issue

  • 1