Open AccessSmall 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
Author(s) -
Li Meng,
Peng Zhongmin,
Ren Wangang,
Wang Zhou
Publication year - 2016
Publication title -
thoracic cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 28
eISSN - 1759-7714
pISSN - 1759-7706
DOI - 10.1111/1759-7714.12356
Subject(s) - pten , tensin , cancer research , transfection , biology , downregulation and upregulation , microbiology and biotechnology , pi3k/akt/mtor pathway , signal transduction , cell culture , biochemistry , gene , genetics
Background Epidermal growth factor receptor‐ t yrosine 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 ( saRNA s) 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.