OncoTargets and Therapy (Jul 2019)

MiR-203 acts as a radiosensitizer of gastric cancer cells by directly targeting ZEB1

  • Jiang Y,
  • Jin S,
  • Tan S,
  • Shen Q,
  • Xue Y

Journal volume & issue
Vol. Volume 12
pp. 6093 – 6104

Abstract

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Ying Jiang, Shan Jin, Shisheng Tan, Qi Shen, Yingbo XueDepartment of Oncology, Guizhou Provincial People‘s Hospital, Guiyang, Guizhou, People’s Republic of ChinaObjective: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Radiotherapy is one of the main strategies for GC treatment, while development of radioresistance limits the effectiveness. microRNA-203 (miR-203) has been reported to participate in progression of GC, whereas its interaction with radiosensitivity of GC and the related mechanism remain largely unclear.Methods: The expressions of miR-203 and zinc finger E-box binding homeobox 1 (ZEB1) were measured in GC tissues and cells by quantitative real-time polymerase chain reaction or western blot. Survival fraction, cell viability and apoptosis were measured in GC cells after treatment of radiation by colony formation, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay or flow cytometry, respectively. Tumor volume and weight were detected in murine xenograft model after radiation treatment. The interaction between miR-203 and ZEB1 was explored by bioinformatics analysis and luciferase activity assay.Results: miR-203 expression was down-regulated and ZEB1 mRNA level was up-regulated in GC. The expression of miR-203 was associated with radiosensitivity of GC cells. Moreover, overexpression of miR-203 decreased survival fraction, cell viability and tumor growth but promoted cell apoptosis in radiation-treated GC cells. However, knockdown of miR-203 played an opposite effect. ZEB1 was validated as a target of miR-203, and it was involved in miR-203-mediated radiosensitivity of GC cells in vitro and in vivo.Conclusion: miR-203 promoted radiosensitivity of GC cells by targeting ZEB1, indicating miR-203 as a promising radiosensitizer for GC treatment.Keywords: gastric cancer, miR-203, ZEB1, radiosensitizer, radiosensitivity

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