SNHG16 regulates invasion and migration of bladder cancer through induction of epithelial-to-mesenchymal transition

Hum Cell. 2020 Jul;33(3):737-749. doi: 10.1007/s13577-020-00343-9. Epub 2020 Mar 24.

Abstract

Bladder cancer (BCa) is one of the most common urinary malignancies in the world. Growing evidence suggests that epithelial-to-mesenchymal transition (EMT) is a major contributor for BCa metastasis. lncRNA small nucleolar RNA host gene 16 (SNHG16) has been reported as a tumor promoter in many cancers. This study aims to investigate the function and mechanism of SNHG16 on EMT in BCa. Quantitative RT-PCR (qRT-PCR) was used to determine the expression of SNHG16 in human BCa tissues and TGF-β-induced cells. Western blot (WB) was performed to evaluate the expression of EMT-related proteins. Transwell assay was exerted to assess the migration and invasion ability of SNHG16 in BCa. RNA pull-down assay was conducted to confirm the RNA-RNA interaction. The precise mechanism by which SNHG16 regulated EMT process in BCa was also explored. SNHG16 was found up-regulated in TGF-β-induced BCa cells and BCa tissues. Transwell assay showed that overexpression of SNHG16 significantly promoted the migration and invasion of BCa cells, whereas knock-down of SNHG16 caused the opposite effects. Then, the interaction between SNHG16 and miR-200a-3p was verified by dual-luciferase reporter assay and RNA pull-down assay. And the effects of knock-down or overexpression of SNHG16 on migration and invasion were reversed by co-transfecting miR-200a-3p inhibitors or mimics. This study first demonstrated that SNHG16 was responsible for EMT of BCa cells via miR-200a-3p/ ZEB1/ZEB2 axis. These results provided a potential therapeutic strategy for BCa treatment, especially in metastatic BCa.

Keywords: Bladder cancer (BCa); Epithelial-to-mesenchymal transition (EMT); Small nucleolar RNA host gene 16 (SNHG16); ZEB1/ZEB2; miR-200a-3p.

MeSH terms

  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression / genetics*
  • Gene Expression Regulation / genetics*
  • Humans
  • MicroRNAs
  • Neoplasm Invasiveness / genetics
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • RNA, Long Noncoding / physiology*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology*
  • Zinc Finger E-box Binding Homeobox 2
  • Zinc Finger E-box-Binding Homeobox 1

Substances

  • MIRN200 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SNHG16 lncRNA, human
  • ZEB1 protein, human
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2
  • Zinc Finger E-box-Binding Homeobox 1