microRNA-137 is downregulated in thyroid cancer and inhibits proliferation and invasion by targeting EGFR

Tumour Biol. 2016 Jun;37(6):7749-55. doi: 10.1007/s13277-015-4611-8. Epub 2015 Dec 22.

Abstract

microRNA-137 expression is downregulated in several tumors. To date, its expression and function in human thyroid cancer remain unexplored. The aim of this study is to identify its expression, function, and molecular mechanism in thyroid cancer. microRNA-137 (miR-137) downregulation was observed in thyroid cancer tissues compared with normal thyroid tissues. miR-137 mimics downregulated B-CPAP cell proliferation, colony formation ability, and invasion, with suppressed expression of cyclin E, MMP2, p-ERK, and p-AKT. miR-137 inhibitor transfection in TPC-1 cell line showed the opposite effects. With prediction software and luciferase reporter assay, we found that epidermal growth factor receptor (EGFR) was a target of miR-137. Transfection of miR-137 mimic suppressed EGFR protein and messenger RNA (mRNA) expression. EGFR small interfering RNA (siRNA) abrogated the role of miR-137 inhibitor on cyclin E, MMP2, p-ERK, and p-AKT. In addition, we found a negative correlation of EGFR and miR-137 in thyroid cancer tissues. In conclusion, the present study showed that miR-137 downregulation is associated with malignant progression of thyroid cancer. miR-137 inhibits growth and invasion by targeting EGFR in thyroid cancer cells.

Keywords: EGFR; Invasion; Proliferation; Thyroid cancer; miR-137.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Cell Division
  • Cell Line, Tumor
  • Down-Regulation
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / biosynthesis
  • ErbB Receptors / genetics*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • RNA Interference
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics*
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Tumor Stem Cell Assay

Substances

  • 3' Untranslated Regions
  • MIRN137 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • RNA, Small Interfering
  • EGFR protein, human
  • ErbB Receptors