Long noncoding RNA PCA3 regulates prostate cancer through sponging miR-218-5p and modulating high mobility group box 1

J Cell Physiol. 2019 Aug;234(8):13097-13109. doi: 10.1002/jcp.27980. Epub 2018 Dec 19.

Abstract

Objective: The purpose of this study was to investigate the mechanism of long noncoding RNA (lncRNA) prostate cancer antigen 3 (PCA3) in prostate cancer (PCa) via regulating the miR-218-5p/high mobility group box 1 (HMGB1) axis.

Methods: The Cancer Genome Atlas database was used to divide differentially expressed lncRNAs, microRNAs, and messenger RNA (mRNAs). The mRNA expressions of lncRNA PCA3, miR-218-5p, and HMGB1 were determined by reverse transcription polymerase chain reaction. Cell propagation was evaluated using the Cell Counting Kit-8 assay and the apoptotic rate was examined by flow cytometry. Cell migration and invasion were observed through the wound healing assay and transwell assay. Target relationships among PCA3, miR-218-5p, and HMGB1 were validated via dual-luciferase reporter gene assay. A nude mouse model in vivo was designed to evaluate the effect of PCA3 on prostate tumor growth.

Results: PCA3 and HMGB1 were high-expressed in PCa, whereas miR-218-5p was low-expressed. PCA3 knockdown or miR-218-5p overexpression suppressed PCa cell proliferation, migration, and invasion, but promoted apoptosis. Besides, targeted relationships and interactions on the expression between miR-218-5p and PCA3 or HMGB1 were elucidated. PCA3 weakened cell viability and mobility whereas induced apoptosis through binding with miR-218-5p. Meanwhile, miR-218-5p also inhibited PCa tumorigenesis via downregulation of HMGB1. Knockdown of PCA3 impeded tumor growth by downregulating its downstream gene HMGB1.

Conclusions: lncRNA PCA3 facilitated PCa progression through sponging miR-218-5p and regulating HMGB1.

Keywords: high mobility group box 1 (HMGB1); long noncoding RNA (lncRNA) prostate cancer antigen 3 (PCA3); miR-218-5p; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / physiology*
  • HMGB1 Protein / genetics
  • HMGB1 Protein / metabolism*
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*
  • RNA, Long Noncoding / genetics

Substances

  • Antigens, Neoplasm
  • HMGB1 Protein
  • HMGB1 protein, human
  • MIRN218 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • prostate cancer antigen 3, human