MicroRNA‑301a targets WNT1 to suppress cell proliferation and migration and enhance radiosensitivity in esophageal cancer cells

Oncol Rep. 2019 Jan;41(1):599-607. doi: 10.3892/or.2018.6799. Epub 2018 Oct 16.

Abstract

Esophageal cancer (EC) is one of the leading causes of death among malignancies. Radiotherapy for esophageal squamous cell carcinoma (ESCC) patients is limited by resistance to ionizing radiation (IR). An increasing body of evidence has demonstrated that aberrant expression of microRNA‑301a (miR‑301a) contributes to cancer progression and sensitivity to radiation. The aim of the present study was to investigate the exact functions and potential mechanisms of miR‑301a in ESCC radioresistance. Initially, the miR‑301a‑transfected radioresistant ESCC cells KYSE‑150R exhibited a decreased proliferation rate, and enhanced radiosensitivity and migration, whereas downregulation of miR‑301a in radiosensitive KYSE‑150 cells produced the opposite results. miR‑301a regulates WNT1 expression at both the mRNA and protein levels. Furthermore, dual‑luciferase reporter assays revealed that WNT1 was a target gene of miR‑301a. In addition, the expression of miR‑301a markedly affected the expression of Wnt/β‑catenin‑related proteins such as β‑catenin and cyclin D1. Finally, overexpression of miR‑301a inhibited epithelial‑mesenchymal transition (EMT) conversion by directly targeting Snail and vimentin in radioresistant‑ESCC cell lines; however, no inhibitory effects were exerted on Twist. Collectively, these results indicated that miR‑301a increased the radiosensitivity and inhibited the migration of radioresistant‑ESCC cells by targeting WNT1, thereby inactivating the Wnt/β‑catenin signaling pathway and EMT reversal. Thus, miR‑301a may be a potential therapeutic target for the treatment of EC radioresistance.

MeSH terms

  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Cyclin D1 / genetics
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Humans
  • MicroRNAs / genetics*
  • Radiation Tolerance / genetics*
  • Signal Transduction / genetics
  • Wnt1 Protein / genetics*
  • beta Catenin / genetics

Substances

  • MicroRNAs
  • WNT1 protein, human
  • Wnt1 Protein
  • beta Catenin
  • Cyclin D1