Liu Zhen, Mai Chunping, Yang Huiling, Zhen Yan, Yu Xiaoli, Hua Shengni, Wu Qiangyun, Jiang Qinping, Zhang Yajie, Song Xin, Fang Weiyi
Department of Pathology, School of Basic Medicine, Guangzhou Medical University, Guangzhou, China; Cancer Research Institute, Southern Medical University, Guangzhou, China.
J Cell Mol Med. 2014 Aug;18(8):1667-79. doi: 10.1111/jcmm.12317. Epub 2014 Jun 26.
We previously reported and revised the nasopharyngeal epithelium specific protein CCDC19 and identified it as a potential tumour suppressor in nasopharyngeal carcinoma. The purpose of this study was to investigate the involvement of CCDC19 in the pathogenesis of human non-small cell lung cancers (NSCLC). Down-regulated CCDC19 expression was observed in NSCLC tissues and cells compared to normal tissues. However, reduced protein expression did not correlate with the status of NSCLC progression. Instead, we observed that patients with lower CCDC19 expression had a shorter overall survival than did patients with higher CCDC19 expression. Lentiviral-mediated CCDC19 overexpression significantly suppressed cell proliferation and cell cycle transition from G1 to S and G2 phases in NSCLC cells. Knocking down CCDC19 expression significantly restored the ability of cell growth in CCDC19 overexpressing NSCLC cells. Mechanistically CCDC19 functions as a potential tumour suppressor by stimulating miR-184 suppression of C-Myc thus blocking cell growth mediated by the PI3K/AKT/C-Jun pathway. Our studies are the first to demonstrate that reduced expression of CCDC19 is an unfavourable factor in NSCLC.
我们之前报道并修订了鼻咽上皮特异性蛋白CCDC19，并将其鉴定为鼻咽癌中的一种潜在肿瘤抑制因子。本研究的目的是调查CCDC19在人类非小细胞肺癌（NSCLC）发病机制中的作用。与正常组织相比，在NSCLC组织和细胞中观察到CCDC19表达下调。然而，蛋白表达降低与NSCLC进展状态无关。相反，我们观察到CCDC19表达较低的患者总生存期比CCDC19表达较高的患者短。慢病毒介导的CCDC19过表达显著抑制了NSCLC细胞的增殖以及细胞周期从G1期到S期和G2期的转变。敲低CCDC19表达显著恢复了CCDC19过表达的NSCLC细胞的生长能力。从机制上讲，CCDC19通过刺激miR-184对C-Myc的抑制作用，从而阻断由PI3K/AKT/C-Jun途径介导的细胞生长，发挥潜在肿瘤抑制因子的作用。我们的研究首次证明CCDC19表达降低是NSCLC中的一个不利因素。
