miR-363 promotes proliferation and chemo-resistance of human gastric cancer via targeting of FBW7 ubiquitin ligase expression

Oncotarget. 2016 Jun 7;7(23):35284-92. doi: 10.18632/oncotarget.9169.


Dysregulation of microRNA expression is involved in several pathological activities associated with gastric cancer progression and chemo-resistance. However, the role and molecular mechanisms of miR-363 in the progression and chemo-resistance of gastric cancer remain enigmatic. In this study, we validated that miR-363 expression was higher in gastric cancer tissues than in adjacent normal tissues. Multivariate analysis identifies high levels of miR-363 expression as an independent predictor for postoperative recurrence and lower overall survival. Increased miR-363 expression promotes gastric cancer cell proliferation and chemo-resistance through directly targeting the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7). Clinically, our data reveal that overexpression of miR-363 correlates with the poor survival outcomes in patients with gastric cancer, and docetaxel + cisplatin + 5-FU (DCF) regimen response is impaired in patients with miR-363 overexpression. These data suggest that miR-363 may be a potential therapeutic target for gastric cancer and serve as a biomarker for predicting response to DCF regimen treatment.

Keywords: FBW7; chemo-resistance; gastric cancer; microRNA-363; proliferation.

MeSH terms

  • Cell Proliferation
  • Disease Progression
  • Drug Resistance, Neoplasm / genetics*
  • F-Box-WD Repeat-Containing Protein 7 / biosynthesis*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • MicroRNAs / genetics*
  • Prognosis
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*


  • F-Box-WD Repeat-Containing Protein 7
  • FBXW7 protein, human
  • MIRN363 microRNA, human
  • MicroRNAs