Candidate tumour suppressor CCDC19 regulates miR-184 direct targeting of C-Myc thereby suppressing cell growth in non-small cell lung cancers.
Candidate tumour suppressor CCDC19 regulates miR-184 direct targeting of C-Myc thereby suppressing cell growth in non-small cell lung cancers.
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DOI：
10.1111/jcmm.12317
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发表时间：
2014-08
影响因子：
5.3
通讯作者：
Fang W
中科院分区：
文献类型：
--
作者：
Liu Z;Mai C;Yang H;Zhen Y;Yu X;Hua S;Wu Q;Jiang Q;Zhang Y;Song X;Fang W
我们以前报道并修订了鼻咽上皮特异性蛋白CCDC 19，并将其鉴定为鼻咽癌的潜在肿瘤抑制因子。本研究的目的是研究CCDC 19在人非小细胞肺癌（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下调的CCDC 19表达。然而，蛋白表达降低与NSCLC进展状态无关。相反，我们观察到CCDC 19表达较低的患者的总生存期比CCDC 19表达较高的患者短。慢病毒介导的CCDC 19过表达显著抑制NSCLC细胞的细胞增殖和细胞周期从G1期向S期和G2期的转变。敲低CCDC 19表达显著恢复了过表达CCDC 19的NSCLC细胞的细胞生长能力。CCDC 19通过刺激miR-184对C-Myc的抑制，从而阻断PI 3 K/AKT/C-Jun途径介导的细胞生长，在机制上发挥潜在肿瘤抑制剂的作用。我们的研究首次证明CCDC 19表达减少是NSCLC的不利因素。
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.
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影响因子：
3.8
作者：
Wei M;Wang Z;Yao H;Yang Z;Zhang Q;Liu B;Yu Y;Su L;Zhu Z;Gu Q
通讯作者：
Gu Q
影响因子：
5.3
作者：
Huang X;Huang F;Yang D;Dong F;Shi X;Wang H;Zhou X;Wang S;Dai S
通讯作者：
Dai S
影响因子：
9
作者：
通讯作者：
--
影响因子：
64.8
作者：
Gonzalez, S;Klatt, P;Serrano, M
通讯作者：
Serrano, M
影响因子：
4.7
作者：
Simile, MM;De Miglio, MR;Pascale, RM
通讯作者：
Pascale, RM