MicroRNA-519a demonstrates significant tumour suppressive activity in laryngeal squamous cells by targeting anti-carcinoma HuR gene

J Laryngol Otol. 2013 Dec;127(12):1194-202. doi: 10.1017/S0022215113003174. Epub 2013 Dec 3.

Abstract

Objective: This study investigated the expression and functional effects, and related molecular mechanisms, of microRNA-519a in laryngeal squamous cell carcinoma.

Methods: MicroRNA-519a and HuR messenger RNA in laryngeal squamous cell carcinoma were measured using reverse transcription polymerase chain reaction. MicroRNA-519a effects on the growth of human epithelial type 2 cells were tested using an MTT assay. The influence of microRNA-519a on the expression levels of HuR and other related genes in protein was tested by Western blotting. Cell cycle analyses were performed using flow cytometry. Associations between expression levels and patients' clinical parameters were analysed with Pearson correlation analysis.

Results: Expression of microRNA-519a in laryngeal squamous cell carcinoma tissues was significantly lower than in adjacent non-cancerous tissues. The expression of microRNA-519a was negatively associated with histological differentiation, tumour-node-metastasis stage, lymphatic metastasis and disease-free survival time. After increasing the level of microRNA-519a in laryngeal squamous cell carcinoma human epithelial type 2 cells, cell growth was inhibited and cell cycle was arrested in the G2/M phase. MicroRNA-519a down-regulated HuR gene expression in protein levels without affecting messenger RNA levels.

Conclusion: MicroRNA-519a may function as a tumour suppressor by inhibiting HuR expression, and may serve as a therapeutic target for laryngeal squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology*
  • ELAV Proteins / antagonists & inhibitors*
  • ELAV Proteins / metabolism
  • Flow Cytometry
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / metabolism
  • Laryngeal Neoplasms / mortality
  • Laryngeal Neoplasms / pathology*
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Biomarkers, Tumor
  • ELAV Proteins
  • MIRN519 microRNA, human
  • MicroRNAs