MicroRNA-1258, regulated by c-Myb, inhibits growth and epithelial-to-mesenchymal transition phenotype via targeting SP1 in oral squamous cell carcinoma

J Cell Mol Med. 2019 Apr;23(4):2813-2821. doi: 10.1111/jcmm.14189. Epub 2019 Feb 7.

Abstract

The biological function and underlying mechanism of miR-1258 has seldom been investigated in cancer progression, including in oral squamous cell carcinoma (OSCC). In the current study, we revealed that the expression level of miR-1258 was significantly down-regulated in OSCC tissues and cell lines. Restoration of miR-1258 decreased OSCC cell growth and invasion. The luciferase and Western blot assays revealed that SP1 protein was a downstream target of miR-1258. Overexpression of SP1 dismissed miR-1258's effect on cell growth and invasion. We also revealed that c-Myb inhibited miR-1258 by directly binding at its promoter. In addition, miR-1258 inhibited PI3K/AKT and ERK signalling pathway activity. Taken together, these findings demonstrated that miR-1258 may function as a tumour-suppressive micorRNA in OSCC and suggested that miR-1258 may be a potential therapeutic target for OSCC patients.

Keywords: SP1; c-Myb; miR-1258; oral squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / secondary*
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Phenotype
  • Prognosis
  • Proto-Oncogene Proteins c-myb / genetics
  • Proto-Oncogene Proteins c-myb / metabolism*
  • Signal Transduction
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism*
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • MIRN1258 microRNA, human
  • MYB protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myb
  • Sp1 Transcription Factor
  • SP1 protein, human