miR-184 Inhibits Tumor Invasion, Migration and Metastasis in Nasopharyngeal Carcinoma by Targeting Notch2

Cell Physiol Biochem. 2018;49(4):1564-1576. doi: 10.1159/000493459. Epub 2018 Sep 17.

Abstract

Background/aims: A recent study found that dysregulated microRNA-184 (miR-184) is involved in the proliferation and survival of nasopharyngeal carcinoma (NPC). This study aimed to evaluate the detailed mechanisms of invasion, migration and metastasis of NPC cells.

Methods: Quantitative reverse-transcription PCR (qRT-PCR) and Western blot were used to confirm the expression levels of miR-184 and Notch2. NPC cell invasion and migration were subsequently examined using in vitro cell invasion and wound-healing assays, respectively. MicroRNA (miRNA) target gene prediction databases and dual-luciferase reporter assay were adopted to validate the target genes of miR-184.

Results: MiR-184 was downregulated in the NPC cell lines. The miR-184 inhibitor increased the number of invading NPC cells, whereas miR-184 mimics inhibited the invasive ability of such cells. The protein level of E-cadherin decreased, whereas those of N-cadherin and vimentin increased in the anti-miR-184 group. This result showed that miR-184 inhibited NPC cell invasion and metastasis by regulating EMT progression. MiRNA target gene prediction databases indicated the potential of Notch2 as a direct target gene of miR-184. Such a notion was then validated by results of dual-luciferase reporter assay. Notably, shRNANotch2 restrained the EMT and partially abrogated the inhibitory effects of miR-184 on EMT progression in NPC cells.

Conclusion: MiR-184 functions as a tumour-suppressive miRNA targeting Notch2 and inhibits the invasion, migration and metastasis of NPC.

Keywords: EMT; Invasion; Metastasis; Nasopharyngeal carcinoma; Notch2; miR-184.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Antagomirs / metabolism
  • Cadherins / metabolism
  • Carcinoma / metabolism
  • Carcinoma / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology*
  • Neoplasm Invasiveness
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Receptor, Notch2 / antagonists & inhibitors
  • Receptor, Notch2 / genetics
  • Receptor, Notch2 / metabolism*
  • Vimentin / metabolism

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • Cadherins
  • MIRN184 microRNA, human
  • MicroRNAs
  • NOTCH2 protein, human
  • RNA, Small Interfering
  • Receptor, Notch2
  • Vimentin