Genetic variants in microRNAs predict non-small cell lung cancer prognosis in Chinese female population in a prospective cohort study

Oncotarget. 2016 Dec 13;7(50):83101-83114. doi: 10.18632/oncotarget.13072.

Abstract

To investigate the prognostic effect of microRNA single nucleotide polymorphisms (SNP) on non-small cell lung cancer (NSCLC) patients, 658 female participants from northeast China were enrolled in our prospective cohort study and followed up from 2010 to 2015. C-containing genotypes of miR-149 rs2292832 were associated with better overall survival (OS). The joint effect of miR-149 and miR-196a2 and the joint effect of miR-149 and miR-608 were also observed in our study. To verify the function of miR-149 rs2292832, A549 cell lines were stably transfected with lenti-virus containing miR-149-C vector, miR-149-T vector and empty vector. Cells containing C allele assumed a higher expression level of miR-149, a decrease in cell growth and the sensitivity to anticancer drug when compared with cells containing T allele. The role of miR-149 playing in cancer prognosis may function through DNA topoisomerases 1 (TOP1) pathway, according to the results from luciferase reporter assays. In conclusion, miR-149 C allele may be a prognostic biomarker for better NSCLC OS.

Keywords: Chinese; SNP; lung cancer; miRNA; prognosis.

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / pharmacology
  • Asian People / genetics
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / ethnology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Cell Proliferation / drug effects
  • China
  • Cisplatin / pharmacology
  • DNA Topoisomerases, Type I / genetics
  • DNA Topoisomerases, Type I / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / ethnology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / therapy
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Risk Factors
  • Sex Factors
  • Time Factors
  • Transfection

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • MIRN149 microRNA, human
  • MIRN196 microRNA, human
  • MIRN608 microRNA, human
  • MicroRNAs
  • DNA Topoisomerases, Type I
  • TOP1 protein, human
  • Cisplatin