Reciprocal effects between microRNA-140-5p and ADAM10 suppress migration and invasion of human tongue cancer cells

Biochem Biophys Res Commun. 2014 Jun 6;448(3):308-14. doi: 10.1016/j.bbrc.2014.02.032. Epub 2014 Feb 13.

Abstract

ADAM10, overexpressed in tongue squamous cell carcinoma (TSCC), has been well documented for its role in tumor progression and metastasis. In the present study, we evaluated the inhibition effect of microRNAs (miRNAs) on the TSCC and identified that miR-140-5p could directly targets ADAM10 and inhibits the invasion and migration of TSCC cells. LAMC1, HDAC7 and PAX6, clustered into migration-related genes, were validated to be direct targets of miR-140-5p, while IGF1R and PSEN1 were not responsible to the regulation. Most intriguingly, ERBB4 was upregulated by miR-140-5p even though the interaction between ERBB4 3'UTR and miR-140-5p existed simultaneously. Meanwhile, ADAM10 is involved in the "positive" regulation of ERBB4 and negative regulation of PAX6 by miR-140-5p. Taken together, our results suggest that miR-140-5p play a role in TSCC cell migration and invasion, and two brand new relationships between miRNA and its targets emerged: (1) ADAM10 is not just a direct target of miR-140-5p, the repressed ADAM10 also helps to enhance the effect of miR-140-5p to other target genes: ERBB4 and PAX6; (2) ERBB4 is "positively" regulated by miR-140-5p.

Keywords: ADAM10; ERBB4; MicroRNA; Tongue squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • ADAM Proteins / antagonists & inhibitors
  • ADAM Proteins / genetics*
  • ADAM Proteins / metabolism
  • ADAM10 Protein
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors
  • Amyloid Precursor Protein Secretases / genetics*
  • Amyloid Precursor Protein Secretases / metabolism
  • Base Sequence
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • ErbB Receptors / genetics
  • Eye Proteins / genetics
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Homeodomain Proteins / genetics
  • Humans
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / prevention & control
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • RNA, Small Interfering / genetics
  • Receptor, ErbB-4
  • Repressor Proteins / genetics
  • Tongue Neoplasms / genetics*
  • Tongue Neoplasms / metabolism
  • Tongue Neoplasms / pathology*

Substances

  • 3' Untranslated Regions
  • Eye Proteins
  • Homeodomain Proteins
  • Membrane Proteins
  • MicroRNAs
  • Mirn140 microRNA, human
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • RNA, Neoplasm
  • RNA, Small Interfering
  • Repressor Proteins
  • ERBB4 protein, human
  • ErbB Receptors
  • Receptor, ErbB-4
  • Amyloid Precursor Protein Secretases
  • ADAM Proteins
  • ADAM10 Protein
  • ADAM10 protein, human