title: Small activating ribonucleic acid reverses tyrosine kinase inhibitor resistance in epidermal growth factor receptor-mutant lung cancer by increasing the expression of phosphatase and tensin homolog.
abstract: BACKGROUND
  Epidermal growth factor receptor-tyrosine kinase inhibitors (TKI-EGFRs) present a new prospect for the treatment of lung cancer. However, in clinical application, the majority of patients become TKI resistant within a year. More and more studies have shown that a loss of phosphatase and tensin homolog (PTEN) expression is associated with TKI resistance. An alternative method of upregulating PTEN expression may reverse TKI resistance.
  
  
  METHODS
  We designed five candidate small activating ribonucleic acids (saRNAs) to target PTEN, and transfected them into H-157 cells to screen out functional saRNA. We used reverse transcriptase-polymerase chain reaction and Western blot to evaluate the effect of saRNA to PTEN expression. We then analyzed the growth and apoptosis of cells transfected with saRNA under the treatment of TKI to investigate whether saRNAs can reverse TKI resistance by upregulating PTEN expression.
  
  
  RESULTS
  The functional saRNA we designed could upregulate PTEN expression. The H-157 cells transfected with saRNA grew slower in the presence of TKI drugs than the cells that were not transfected with saRNA. The apoptosis rate was also obviously higher.
  
  
  CONCLUSIONS
  Our study proves that loss of PTEN expression is an important mechanism of TKI resistance. It is possible to control TKI resistance by upregulating PTEN expression using RNA activation technology.
authors.affiliation: Department of Thoracic Surgery Provincial Hospital Affiliated to Shandong University, Shandong University Jinan China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery Provincial Hospital Affiliated to Shandong University, Shandong University Jinan China.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Thoracic Surgery Provincial Hospital Affiliated to Shandong University, Shandong University Jinan China.
authors.forename: Wangang
authors.initials: W
authors.lastname: Ren
authors.affiliation: Department of Thoracic Surgery Provincial Hospital Affiliated to Shandong University, Shandong University Jinan China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wang
keywords: Epidermal growth factor receptor; non‐small cell lung cancer; phosphatase and tensin homolog; ribonucleic acid activation; tyrosine kinase inhibitors