Gene expression profiling of taxol-resistant nasopharyngeal carcinoma cells with siRNA-mediated FOLR1 downregulation

Int J Clin Exp Pathol. 2015 Sep 1;8(9):11314-22. eCollection 2015.

Abstract

Objectives: Our previous study has shown that downregulation of FOLR1 by siRNA partially reversed taxol-resistant phenotype in taxol-resistant nasopharyngeal carcinoma cell lines. We aim to gain further insight into the molecular mechanisms of this process and identify the differentially expressed genes after FOLR1 downregulation.

Method: The global gene expression profile was identified and analyzed using the Affymetrix HG-U133 Plus 2.0 array.

Results: There was a significant dysregulation in the global gene expression of the FOLR1-suppressed taxol-resistant nasopharyngeal carcinoma cell lines. There were 41 upregulated genes and 109 downregulated genes. QRT-PCR validation of the selected differentially expressed genes demonstrated there was a good correlation with the microarray analysis. There was a significant deregulation of expression in the apoptosis-related genes such as BIRC3, PRKX, TNFRSF10A and involved in Viral carcinogenesis, MAPK signaling pathways after FOLR1 was downregulated.

Conclusion: The suppression of FOLR1 by RNA interference altered gene expression profile of taxol-resistant nasopharyngeal carcinoma cell lines. The apoptosis-related genes and the gene alterations in viral carcinogenesis, MAPK signaling pathways might be important in FOLR1 siRNA-induced taxol-resistant reversal.

Keywords: FOLR1; Gene expression profiling; nasopharyngeal carcinoma; signaling pathway; small interfering RNA; taxol resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Transformation, Viral / genetics
  • Cluster Analysis
  • Down-Regulation
  • Drug Resistance, Neoplasm / genetics*
  • Folate Receptor 1 / genetics*
  • Folate Receptor 1 / metabolism
  • Gene Expression Profiling* / methods
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MAP Kinase Signaling System / genetics
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • Oligonucleotide Array Sequence Analysis
  • Paclitaxel / pharmacology*
  • RNA Interference*
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • Transfection

Substances

  • Antineoplastic Agents, Phytogenic
  • FOLR1 protein, human
  • Folate Receptor 1
  • RNA, Small Interfering
  • Paclitaxel