Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Jiao Chang Dong Lu 32, 650223, Kunming, China.
Kunming College of Life Science, University of Chinese Academy of Sciences, 100049, Beijing, China.
Cell Death Dis. 2018 Feb 20;9(3):295. doi: 10.1038/s41419-018-0299-1.
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.
肺癌是全球癌症相关死亡的主要原因，非小细胞肺癌（NSCLC）约占所有病例的 80%，是肺癌的主要亚组。已经证明 G 蛋白偶联受体激酶 5（GRK5）在包括癌症在内的几种病理状况的发展和进展中发挥着关键作用。在这里，我们通过免疫组织化学分析发现，GRK5 在 539 个 NSCLC 癌组织中的表达明显高于 99 个正常非癌组织；我们还表明，在女性和腺癌（ADC）NSCLC 患者中，GRK5 阳性染色百分比明显高于男性和鳞状细胞癌（SCC）患者。此外，GRK5 高表达 NSCLC 患者的总生存率低于低表达患者。我们提供的证据表明，与正常的人支气管上皮细胞系（BEAS-2B）相比，GRK5 的 mRNA 和蛋白表达水平在 NSCLC 癌细胞系（GLC-82、SPC-A-1、H520、H838、H358、A549 和 H1299）中均升高，并且在 NSCLC 癌组织中发现了许多 GRK5 突变。此外，我们发现 GRK5 的耗竭抑制了 NSCLC 癌细胞的体外增殖、迁移，并在体内抑制了异种移植肿瘤的形成。此外，GRK5 敲低促进了细胞周期停滞在 G2/M 期，并诱导了细胞凋亡。总之，我们的数据揭示了 GRK5 在 NSCLC 进展中的致癌作用，表明 GRK5 可能在未来成为新的治疗靶点。
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