Role of mir-96/EVI1/mir-449a axis in the nasopharyngeal carcinoma cell migration and tumor sphere formation

Lai Sheung Chan, Hong Lok LUNG, Roger Kai Cheong Ngan, Anne Wing Mui Lee, Sai Wah Tsao, Kwok Wai Lo, Michael Kahn, Maria Li Lung, Rotraud Wieser, Nai Ki MAK*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The Wnt signaling pathway is one of the major signaling pathways used by cancer stem cells (CSC). Ecotropic Viral Integration Site 1 (EVI1) has recently been shown to regulate oncogenic development of tumor cells by interacting with multiple signaling pathways, including the Wnt signaling. In the present study, we found that the Wnt modulator ICG-001 could inhibit the expression of EVI1 in nasopharyngeal carcinoma (NPC) cells. Results from loss-of-function and gain-of-function studies revealed that EVI1 expression positively regulated both NPC cell migration and growth of CSC-enriched tumor spheres. Subsequent studies indicated ICG-001 inhibited EVI1 expression via upregulated expression of miR-96. Results from EVI1 3′UTR luciferase reporter assay confirmed that EVI1 is a direct target of miR-96. Further mechanistic studies revealed that ICG-001, overexpression of miR-96, or knockdown of EVI1 expression could restore the expression of miR449a. The suppressive effect of miR-449a on the cell migration and tumor sphere formation was confirmed in NPC cells. Taken together, the miR-96/EVI1/miR-449a axis is a novel pathway involved in ICG-001-mediated inhibition of NPC cell migration and growth of the tumor spheres.

Original languageEnglish
Article number5495
Pages (from-to)1-15
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume21
Issue number15
DOIs
Publication statusPublished - 1 Aug 2020

Scopus Subject Areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

User-Defined Keywords

  • EVI1
  • ICG-001
  • MiR-449a
  • MiR-96
  • Nasopharyngeal carcinoma

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