MicroRNA-199a-3p suppresses the invasion and metastasis of nasopharyngeal carcinoma through SCD1/PTEN/AKT signaling pathway

Cell Signal. 2023 Oct:110:110833. doi: 10.1016/j.cellsig.2023.110833. Epub 2023 Aug 4.

Abstract

MicroRNAs (miRs) are 18-25 nucleotides non-coding RNAs, which contribute to tumorigenesis. Previous studies have demonstrated that miR-199a-3p is dysregulated in human nasopharyngeal carcinoma (NPC), but its role in NPC progression still largely unknown. The current study aimed to determine the potential role of miR-199a-3p in NPC progression and the underlying mechanisms. In this study, miR-199a-3p was found to be prominently down-regulated in NPC tissues and cells. The cellular assay showed that transfection of miR-199a-3p markedly repressed the migration, invasion and induced epithelial-mesenchymal transition (EMT) in both 5-8F and CNE-2 cell lines. By dual-luciferase reporter, western blotting and gas chromatography assays, we found that SCD1 is not only highly expressed in NPC tissues and negatively associated with the prognosis of NPC patients but also can be apparently downregulated by miR-199a-3p in NPC cells, suggesting that SCD1 is a direct target gene of miR-199a-3p. Moreover, inhibition of miR-199a-3p expression activated PI3K/Akt signaling and up-regulated the expression of MMP-2. With tumor xenograft models in nude mice, we also showed that miR-199a-3p repressed tumor growth in vivo. Our study demonstrated that miR-199a-3p inhibited migration and invasion of NPC cells through downregulating SCD1 expression, thus providing a potential target for the treatment of NPC.

Keywords: Fatty acid metabolism; Invasion; Migration; NPC; SCD1; miR-199a-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Nasopharyngeal Carcinoma / genetics
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Neoplasms* / genetics
  • Nasopharyngeal Neoplasms* / pathology
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / genetics
  • Stearoyl-CoA Desaturase / genetics
  • Stearoyl-CoA Desaturase / metabolism

Substances

  • MicroRNAs
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • SCD1 protein, human
  • Stearoyl-CoA Desaturase
  • mirn199 microRNA, human