CCDC106 promotes non-small cell lung cancer cell proliferation.
CCDC106 promotes non-small cell lung cancer cell proliferation.
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CCDC106促进非小细胞肺癌细胞增殖
DOI：
10.18632/oncotarget.15792
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发表时间：
2017-04-18
期刊：
影响因子：
--
通讯作者：
Wang E
中科院分区：
文献类型：
--
作者：
Zhang X;Zheng Q;Wang C;Zhou H;Jiang G;Miao Y;Zhang Y;Liu Y;Li Q;Qiu X;Wang E
卷曲螺旋结构域（CCDC）家族成员增强肿瘤细胞增殖，高CCDC蛋白水平与不利的肿瘤相关。有限的研究表明，CCDC 106可能促进p53/TP 53蛋白的降解并抑制其反式活性。本研究显示，在183例非小细胞肺癌中，CCDC 106表达与TNM分期（P = 0.008）、区域淋巴结转移（P < 0.001）和总生存率（P < 0.001）相关。分别选择A549和H1299细胞作为CCDC 106低表达和CCDC 106高表达细胞系的代表。CCDC 106过表达促进A549细胞增殖和裸小鼠异种移植瘤生长，而SiRNA介导的CCDC 106敲低抑制H1299细胞增殖。CCDC 106促进AKT磷酸化，上调细胞周期调节蛋白Cyclin A2和Cyclin B1。CCDC 106通过细胞周期蛋白A2和细胞周期蛋白B1促进的细胞增殖通过用AKT抑制剂LY 294002处理而得到挽救。我们的研究表明，CCDC 106与非小细胞肺癌的进展和不良预后相关。CCDC 106可增强A549和H1299细胞Cyclin A2和Cyclin B1的表达，促进细胞增殖，其作用依赖于AKT信号通路。这些结果表明，CCDC 106可能是肺癌治疗的新靶点。
Coiled-coil domain containing (CCDC) family members enhance tumor cell proliferation, and high CCDC protein levels correlate with unfavorable prognoses. Limited research demonstrated that CCDC106 may promote the degradation of p53/TP53 protein and inhibit its transactivity. The present study demonstrated that CCDC106 expression correlates with advanced TNM stage (P = 0.008), positive regional lymph node metastasis (P < 0.001), and poor overall survival (P < 0.001) in 183 non-small cell lung cancer cases. A549 and H1299 cells were selected as representative of CCDC106-low and CCDC106-high expressing cell lines, respectively. CCDC106 overexpression promoted A549 cell proliferation and xenograft tumor growth in nude mice, while siRNA-mediated CCDC106 knockdown inhibited H1299 cell proliferation. CCDC106 promoted AKT phosphorylation and upregulated the cell cycle-regulating proteins Cyclin A2 and Cyclin B1. Cell proliferation promoted by CCDC106 via Cyclin A2 and Cyclin B1 was rescued by treatment with the AKT inhibitor, LY294002. Our studies revealed that CCDC106 is associated with non-small cell lung cancer progression and unfavorable prognosis. CCDC106 enhanced Cyclin A2 and Cyclin B1 expression and promoted A549 and H1299 cell proliferation, which depended on AKT signaling. These results suggest that CCDC106 may be a novel target for lung cancer treatment.