Upregulation of miR-519 enhances radiosensitivity of esophageal squamous cell carcinoma trough targeting PI3K/AKT/mTOR signaling pathway

Cancer Chemother Pharmacol. 2019 Dec;84(6):1209-1218. doi: 10.1007/s00280-019-03922-2. Epub 2019 Sep 16.

Abstract

Purpose: MicroRNA-519 (miR-519) has been previously reported to function as a tumor suppressor in several types of malignancies. This study aimed to probe the biological role of miR-519 in esophageal squamous cell carcinoma (ESCC).

Methods: qRT-PCR was utilized to test the miR-519 expression level in ESCC tissues and cells. Clinical value of miR-519 was investigated by Kaplan-Meier method. Function assays were conducted to determine the role of miR-519 in radioresistance of ESCC cells. The miR-519-regulated pathways were determined by Kyoto Encyclopedia of Genes and Genomes pathway analysis.

Results: Low expression level of miR-519 was closely correlated with the poor prognosis for overall survival of ESCC patients or patients who received radiotherapy. Functional assays indicated that upregulation of miR-519 made ESCC cells more sensitive to γ-ray radiation and facilitated ESCC cell apoptosis triggered by irradiation treatment via regulating DNA response. Ectopic expression of miR-519 decreased the level of p-AKT and p-mTOR, thus inactivating PI3K/AKT/mTOR signaling pathway after irradiation.

Conclusion: These observations elucidated that upregulated miR-519 is closely correlated with the radiosensitivity of ESCC cells, which may contribute to finding a new promising target for improving the efficiency of radiotherapy in patients with ESCC.

Keywords: ESCC; PI3K/AKT/mTOR; Radiosensitivity; miR-519.

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Apoptosis / genetics
  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Proliferation / radiation effects
  • Chemoradiotherapy, Adjuvant
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / therapy*
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / mortality
  • Esophageal Squamous Cell Carcinoma / pathology
  • Esophageal Squamous Cell Carcinoma / therapy*
  • Esophagectomy
  • Esophagus / pathology
  • Esophagus / radiation effects
  • Esophagus / surgery
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • MicroRNAs / metabolism*
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Radiation Tolerance / genetics*
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Antineoplastic Agents
  • MIRN519 microRNA, human
  • MicroRNAs
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases