AGAP2-AS1/miR-628-5p/FOXP2 feedback loop facilitates the growth of prostate cancer via activating WNT pathway

Carcinogenesis. 2021 Oct 26;42(10):1270-1280. doi: 10.1093/carcin/bgab062.

Abstract

Increasing studies have indicated the critical roles of long non-coding RNAs (lncRNAs) in the tumorigenesis of cancers. LncRNA AGAP2 antisense RNA 1 (AGAP2-AS1) can serve as an oncogenic role in some cancers, including prostate cancer (PCa). However, the underling mechanism of such lncRNA in PCa has not been fully studied. Therefore, it is meaningful to investigate the role and underlying mechanism of AGAP2-AS1 in PCa. AGAP2-AS1 was confirmed to be highly expressed in PCa cells. Functionally, AGAP2-AS1 silencing inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition process and induced apoptosis. According to mechanism assays, AGAP2-AS1 sponged miR-628-5p, which was found to restrain PCa cell growth. Besides, FOXP2 was identified as a target gene of miR-628-5p, and its expression was negatively regulated by miR-628-5p and positively modulated by AGAP2-AS1. Importantly, we found that FOXP2 could function as the upstream gene of AGAP2-AS1. Through rescue experiments, we discovered that FOXP2 up-regulation countered AGAP2-AS1 knockdown-mediated inhibition on PCa cell growth. Finally, it was found that AGAP2-AS1 could activate WNT pathway, and LiCl could reverse the influence of AGAP2-AS1 on PCa biological behaviors. To conclude, AGAP2-AS1/miR-628-5p/FOXP2 feedback loop facilitated PCa cell growth via activating WNT pathway.

MeSH terms

  • Antisense Elements (Genetics) / genetics*
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition
  • Forkhead Transcription Factors / metabolism*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Humans
  • Male
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Wnt Signaling Pathway*

Substances

  • Antisense Elements (Genetics)
  • FOXP2 protein, human
  • Forkhead Transcription Factors
  • GTPase-Activating Proteins
  • MIRN628 microRNA, human
  • MicroRNAs
  • AGAP2 protein, human
  • GTP-Binding Proteins