DLX6-AS1 accelerates cell proliferation through regulating miR-497-5p/SNCG pathway in prostate cancer

Environ Toxicol. 2021 Mar;36(3):308-319. doi: 10.1002/tox.23036. Epub 2020 Oct 9.

Abstract

Prostate cancer (PCa) has become the second leading cause of cancer-related mortality in males worldwide. Although the long noncoding RNA DLX6-AS1 has been recognized to be an oncogene in multiple cancers, the biological function and regulatory mechanism of DLX6-AS1 in prostate cancer are still obscure. In the present study, we observed that DLX6-AS1 was significantly upregulated in PCa tissues and cells. Knockdown of DLX6-AS1 inhibited PCa progression by suppressing cell proliferation and accelerating cell apoptosis. Molecular mechanism exploration indicated that DLX6-AS1 acted as a sponge for miR-497-5p and synuclein gamma (SNCG) was a downstream target gene of miR-497-5p. In addition, there was a negative correlation between DLX6-AS1 and miR-497-5p in PCa tissues. Rescue assays showed that SNCG overexpression could partially recover DLX6-AS1 knockdown-mediated inhibition of progression in PCa. Furthermore, xenograft tumor model was established to determine the role of DLX6-AS1 in PCa tumor growth and the results suggested that DLX6-AS1 could facilitate tumor growth by regulating SNCG in vivo. In conclusion, our study investigated the biological function and underlying mechanism of DLX6-AS1 in PCa and validated that DLX6-AS1 functioned as an oncogene through miR-497-5p/SNCG axis.

Keywords: DLX6-AS1; SNCG; miR-497-5p; prostate cancer.

MeSH terms

  • Apoptosis
  • Cell Proliferation / genetics*
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • MicroRNAs / metabolism*
  • Neoplasm Proteins / genetics
  • Prostatic Neoplasms / genetics*
  • RNA, Long Noncoding / genetics
  • Up-Regulation
  • gamma-Synuclein / genetics
  • gamma-Synuclein / metabolism

Substances

  • DLX6 protein, human
  • Homeodomain Proteins
  • MIRN497 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Long Noncoding
  • SNCG protein, human
  • gamma-Synuclein