@Article{096504017X15144755633680,
AUTHOR = {Ning Wang, Tingting Zhang},
TITLE = {Downregulation of MicroRNA-135 Promotes Sensitivity of Non-Small  Cell Lung Cancer to Gefitinib by Targeting TRIM16},
JOURNAL = {Oncology Research},
VOLUME = {26},
YEAR = {2018},
NUMBER = {7},
PAGES = {1005--1014},
URL = {http://www.techscience.com/or/v26n7/56714},
ISSN = {1555-3906},
ABSTRACT = {Personalized treatment targeting the epidermal growth factor receptor (EGFR) may be a promising new 
treatment of non-small cell lung cancer (NSCLC). Gefitinib, a tyrosine kinase inhibitor, is the first drug for 
NSCLC, which unfortunately easily leads to drug resistance. Our study aimed to explore the functional role of 
microRNA (miR)-135 in the sensitivity to gefitinib of NSCLC cells. Expression of miR-135 in normal cells 
and NSCLC cells was assessed, followed by the effects of abnormally expressed miR-135 on cell viability, 
migration, invasion, apoptosis, sensitivity to gefitinib, and the expression levels of adhesion molecules and 
programmed death ligand 1 (PD-L1) in H1650 and H1975 cells. Next, the possible target gene of miR-135 
was screened and verified. Finally, the potential involvement of the JAK/STAT signaling pathway was investigated. Expression of miR-135 was upregulated in NSCLC cells, and miR-135 silencing repressed cell viability, 
migration, and invasion, but increased cell apoptosis and sensitivity to gefitinib. E-cadherin and β-catenin 
were significantly upregulated, but PD-L1 was downregulated by the silencing of miR-135. Subsequently, 
tripartite-motif (TRIM) 16 was screened and verified to be a target gene of miR-135, and miR-135 suppression 
was shown to function through upregulation of TRIM16 expression. Phosphorylated levels of the key kinases 
in the JAK/STAT pathway were reduced by silencing miR-135 by targeting TRIM16. In conclusion, miR-135 
acted as a tumor promoter, and its suppression could improve sensitivity to gefitinib by targeting TRIM16 and 
inhibition of the JAK/STAT pathway.},
DOI = {10.3727/096504017X15144755633680}
}