LncRNA NEAT1 antagonizes the inhibition of melanoma proliferation, migration, invasion and EMT by Polyphyllin B

Naunyn Schmiedebergs Arch Pharmacol. 2023 Oct;396(10):2469-2480. doi: 10.1007/s00210-023-02474-w. Epub 2023 Apr 1.

Abstract

Polyphyllin B (PPB) is a compound with anti-tumor effects. Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long-stranded noncoding RNA that induces epithelial-mesenchymal transition (EMT) of tumor cells and promotes tumor growth and metastasis. However, the role and mechanism of PPB on melanoma and the correlation between them remain unclear. In this study we screened NEAT1 by using LncRNA transcriptomic sequencing, and then transfected B16F10 cells using OVER-NEAT1 lentivirus. Next, we found that PPB had significant proliferation inhibition of melanoma and B16F10 cells through MTT assay and establishment of mouse subcutaneous transplantation tumor model; in addition, through wound healing assay, transwell assay and establishment of mouse melanoma lung metastasis model, we found that PPB significantly inhibited the invasion and migration of B16F10 cells in vitro, and inhibited the metastasis of melanoma to lung, bone and liver in vivo. Finally, changes in the expression levels of EMT-related proteins were assessed by western blot (WB) and immunohistochemistry, and PPB significantly downregulated the expression levels of MMP-9, N-cadherin, etc., and upregulated E-cadherin. While overexpressed NEAT1 showed the ability to promote melanoma proliferation, migration and invasion, in addition to partially reversed the inhibition of proliferation, migration and invasion of melanoma by PPB mentioned above.

Keywords: Nuclear paraspeckle assembly transcript 1; Polyphyllin B; epithelial-mesenchymal transition; invasion and migration; melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Melanoma* / genetics
  • Mice
  • MicroRNAs* / genetics
  • Neoplasm Invasiveness
  • RNA, Long Noncoding* / metabolism

Substances

  • RNA, Long Noncoding
  • MicroRNAs