Abstract
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.
Highlights
1234567890():,; 1234567890():,; Abstract 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
In order to examine the functional roles of G protein-coupled receptor kinase 5 (GRK5) in NSCLC, we firstly investigated the correlation between the expression of GRK5 protein and clinicopathological features of NSCLC, and applied immunohistochemistry (IHC) in the NSCLC tissue microarray (TMA) (Fig. 1a–c) that contained 539 NSCLC cancerous tissues and 99 normal or noncancerous tissues
We found that the percentage of positive intensive GRK5 expression is significantly higher in NSCLC cancerous tissues (70.3%; 379/539) than that in normal lung tissues (45.5%; 45/99), higher in ADC (75.3%; 219/291) and female (76.1%; 108/142) cancerous tissues than that in squamous cell carcinoma (SCC) (64.5%; 160/248) and male (68.3%; 271/397) cancerous tissues, respectively (Fig. 1d)
Summary
1234567890():,; 1234567890():,; Abstract 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. GRK5 was identified to phosphorylate nucleophosmin (NPM1), regulating sensitivity to polo-like kinase inhibitor-induced apoptosis of breast cancer cells[21], and its upregulation mediated by tazaroteneinduced gene 1 (TIG1) significantly suppresses colon cancer growth[22]. It is still unclear whether GRK5 plays any role during NSCLC tumor progression
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