Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain.
Pathology Department, Hospital Universitari General de Catalunya, Sant Cugat del Vallès, Barcelona, Spain.
Sci Rep. 2017 Aug 31;7(1):10228. doi: 10.1038/s41598-017-10770-8.
As lung cancer has increased to the most common cause of cancer death worldwide, prognostic biomarkers and effective targeted treatments remain lacking despite advances based on patients' stratification. Multiple core cyclins, best known as drivers of cell proliferation, are commonly deregulated in lung cancer where they may serve as oncogenes. The recent expansion of the cyclin family raises the question whether new members might play oncogenic roles as well. Here, we investigated the protein levels of eight atypical cyclins in lung cancer cell lines and formalin-fixed and paraffin-embedded (FFPE) human tumors, as well as their functional role in lung cancer cells. Of the new cyclins evaluated, CNTD2 was significantly overexpressed in lung cancer compared to adjacent normal tissue, and exhibited a predominant nuclear location. CNTD2 overexpression increased lung cancer cell viability, Ki-67 intensity and clonogenicity and promoted lung cancer cell migration. Accordingly, CNTD2 enhanced tumor growth in vivo on A549 xenograft models. Finally, the analysis of gene expression data revealed a high correlation between elevated levels of CNTD2 and decreased overall survival in lung cancer patients. Our results reveal CNTD2 as a new oncogenic driver in lung cancer, suggesting value as a prognostic biomarker and therapeutic target in this disease.
由于肺癌已成为全球最常见的癌症死因，尽管基于患者分层的治疗方法取得了进展，但仍缺乏预后生物标志物和有效的靶向治疗方法。多种核心细胞周期蛋白作为细胞增殖的驱动因子，在肺癌中通常失调，它们可能作为癌基因发挥作用。细胞周期蛋白家族的最近扩展提出了一个问题，即新成员是否也可能发挥致癌作用。在这里，我们研究了八种非典型细胞周期蛋白在肺癌细胞系和福尔马林固定石蜡包埋（FFPE）人类肿瘤中的蛋白水平，以及它们在肺癌细胞中的功能作用。在所评估的新细胞周期蛋白中，CNTD2 在肺癌中与相邻正常组织相比明显过表达，并表现出主要的核定位。CNTD2 过表达增加了肺癌细胞的活力、Ki-67 强度和集落形成能力，并促进了肺癌细胞的迁移。因此，CNTD2 增强了 A549 异种移植模型中的体内肿瘤生长。最后，基因表达数据分析显示，CNTD2 水平升高与肺癌患者总生存率降低之间存在高度相关性。我们的研究结果揭示了 CNTD2 作为肺癌中的一个新的致癌驱动因子，表明其作为该疾病的预后生物标志物和治疗靶点具有价值。
