MiR-34a inhibits the proliferation, migration, and invasion of oral squamous cell carcinoma by directly targeting SATB2

J Cell Physiol. 2020 May;235(5):4856-4864. doi: 10.1002/jcp.29363. Epub 2019 Oct 29.

Abstract

In various kinds of carcinomas, the special AT-rich sequence-binding protein 2 (SATB2) with its atypical expression promotes the metastasis and progression of the tumor, though in the oral squamous cell carcinoma (OSCC) its inherent mechanism and the status of SATB2 remain unclear. The role played by the SATB2 expression in the OSCC cell lines and tissue samples in the target of miR-34a downstream is the intended endeavor of this study. In te OSCCs the miR-34a expression was determined by quantitative real-time polymerase chain reaction (q-PCR), while the SATB2 expression in the cell lines and tissue samples in OSCC was analyzed with the q-PCR and the western blot. Studies in both in vitro and in vivo of the effects of miR-34a on the initiation of OSCC were conducted. As a direct target of the miR-34a the SATB2 was verified with the luciferase reporter assay. In cases where the miR-34a levels were low, the SATB2 in OSCCs seemed to be overexpressed. Besides, both in the in vitro and in vivo a suppression of migration, invasion, and cell growth was caused by miR-34a by down regulating the SATB2 expression. The SATB2 being a direct target of miR-34a was confirmed by the cotransfection of miR-34a mimics specifically the decrease in the expression of luciferase of SATB2-3'UTR-wt reporter. As a whole, our study confirmed the inhibition of miR-34a in the invasion, proliferation, and migration of the OSCCs, playing a potential tumor suppressor role with SATB2 as its downstream target.

Keywords: OSCC; SATB2; dual-luciferase; miR-34a; tumor suppressor gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Matrix Attachment Region Binding Proteins / genetics
  • Matrix Attachment Region Binding Proteins / metabolism*
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Neoplasm Invasiveness
  • Signal Transduction
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Burden

Substances

  • MIRN34 microRNA, human
  • Matrix Attachment Region Binding Proteins
  • MicroRNAs
  • SATB2 protein, human
  • Transcription Factors