Correlation between the expression of miR150 and FOXO4 and the local recurrence and metastasis of nasopharyngeal carcinoma after intensive radiotherapy

J BUON. 2018 Nov-Dec;23(6):1671-1678.

Abstract

Purpose: To investigate the relationship between the expression of miR150 and FOXO4 in nasopharyngeal carcinoma (NPC) and the local recurrence and metastasis after intensive radiotherapy.

Methods: 94 patients with NPC were selected in Hunan Provincial People's Hospital from May 2011 to May 2013. All patients received intensive radiotherapy. Thirty healthy controls were also included. The expression levels of miR150 and FOXO4 mRNA in blood lymphocytes were detected by RT-PCR. All patients with NPC were followed up for 36 months. Blood was drawn from patients to analyze the expression of miR150 and FOXO4. MiR150 inhibitor was used to treat NPC cells, and FOXO4 overexpression cell lines were established. Transwell invasion assay was performed to investigate the effects of miR150 expression inhibition and FOXO4 overexpression on cell invasion. Protein levels were detected by western blot.

Results: Compared with healthy controls, the levels of miR150 mRNA in NPC patients were significantly increased, while FOXO4 mRNA levels were significantly decreased (p<0.05). The levels of miR150 and FOXO4 were significantly correlated with distant metastasis and tumor recurrence (p<0.05). High expression level of miR150 or low expression level of FOXO4 significantly shortened the overall survival (OS) of patients (p<0.05). Cox's proportional hazards model showed that miR150 and FOXO4 were potential independent risk factors for NPC (p<0.05). The level of miR150 in patients with tumor recurrence was significantly higher than that in patients without tumor recurrence, while the level of FOXO4 in patients with tumor recurrence was lower than that patients without tumor recurrence (p<0.05). MiR150 expression inhibition or FOXO4 overexpression significantly reduced the invasion abilities of CNE1 and CNE2 cells and protein levels of matrix metalloproteinase2 (MMP2) and MMP9 (p<0.05).

Conclusion: MiR150 and FOXO4 are closely related to the metastasis and recurrence of NPC, and are independent prognostic factors for NPC. MiR150 and FOXO4 are of clinical significance in predicting NPC prognosis.

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Cell Cycle Proteins
  • Cell Movement
  • Cell Proliferation
  • Female
  • Follow-Up Studies
  • Forkhead Transcription Factors
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Nasopharyngeal Carcinoma / genetics
  • Nasopharyngeal Carcinoma / metabolism
  • Nasopharyngeal Carcinoma / radiotherapy
  • Nasopharyngeal Carcinoma / secondary*
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology*
  • Nasopharyngeal Neoplasms / radiotherapy
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Recurrence, Local / radiotherapy
  • Prognosis
  • Radiotherapy / mortality*
  • Survival Rate
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • FOXO4 protein, human
  • Forkhead Transcription Factors
  • MIRN150 microRNA, human
  • MicroRNAs
  • Transcription Factors