首页> 外文期刊>Journal of cellular and molecular medicine. >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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Candidate tumour suppressor CCDC19 regulates miR‐184 direct targeting of C‐Myc thereby suppressing cell growth in non‐small cell lung cancers

机译:候选肿瘤抑制物CCDC19调节miR‐184直接靶向C‐Myc,从而抑制非小细胞肺癌中的细胞生长

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AbstractWe 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.
机译:摘要我们之前曾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的潜在抑癌基因。这项研究的目的是调查CCDC19参与人类非小细胞肺癌(NSCLC)的发病机制。与正常组织相比,在NSCLC组织和细胞中观察到CCDC19表达下调。但是,减少的蛋白质表达与NSCLC进展状态无关。相反,我们观察到CCDC19表达较低的患者的总生存期比CCDC19表达较高的患者的生存期短。慢病毒介导的CCDC19过表达显着抑制了NSCLC细胞中的细胞增殖和细胞周期从G1期到S和G2期的转变。降低CCDC19的表达可显着恢复CCDC19过表达的NSCLC细胞中细胞生长的能力。从机制上讲,CCDC19通过刺激miR-184抑制C-Myc发挥潜在的肿瘤抑制作用,从而阻断PI3K / AKT / C-Jun途径介导的细胞生长。我们的研究首次证明CCDC19的表达降低是NSCLC中的不利因素。

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