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

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

• miR-184
• Nasopharyngeal carcinoma
• Notch2
• Invasion
• Metastasis
• EMT