Lung cancer is the leading cause of cancer-related deaths worldwide, and non-small-cell lung cancer (NSCLC)
accounts for about 80% of all cases, which is the major subgroup of lung cancer. G protein-coupled receptor kinase 5
(GRK5) has been demonstrated to play pivotal roles in both development and progression of several pathological
conditions including cancer. Here, we found that GRK5 expression was significantly increased in 539 NSCLC cancerous
tissues than that in 99 normal non-cancerous tissues by immunohistochemistry analysis; we also showed intensive
higher positive staining percentage in female and adenocarcinoma (ADC) NSCLC patients than that in male and
squamous cell carcinoma (SCC) patients, respectively. In addition, GRK5 high expression NSCLC patients had a worse
overall survival rate than the low expression patients. We provided evidence showing that both the mRNA and protein
expression levels of GRK5 were increased in NSCLC cancerous cell lines (GLC-82, SPC-A-1, H520, H838, H358, A549, and
H1299) comparing with that in normal human bronchial epithelium cell line (BEAS-2B), and identified many GRK5
mutations in NSCLC cancerous tissues. In addition, we found that depletion of GRK5 inhibited NSCLC cancerous cell
proliferation, migration in vitro, and xenograft tumor formation in vivo. Furthermore, GRK5 knockdown promoted cell
cycle arrest at G2/M phase and induced cellular apoptosis. In summary, our data reveal an oncogenic role of GRK5 in
NSCLC progression, indicating that GRK5 could be used as a new therapeutic target in future.