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卷曲螺旋结构域蛋白 154 通过与微小染色体维持复合物成分 2 相互作用促进结直肠癌的增殖和转移。

Coiled-coil domain-containing 154 promotes colorectal cancer proliferation and metastasis via interacting with minichromosome maintenance complex component 2.

机构信息

Department of Radiation Oncology, Zhongshan Hospital, Fudan University, NO. 180, Fenglin Road, Xuhui District, Shanghai, 200032, People's Republic of China.

Department of Colorectal Surgery, Zhongshan Hospital Fudan University, NO. 180, Fenglin Road, Xuhui District, Shanghai, 200032, People's Republic of China.

出版信息

Cancer Lett. 2023 Dec 1;578:216460. doi: 10.1016/j.canlet.2023.216460. Epub 2023 Oct 19.

Abstract

Coiled-Coil Domain-Containing (CCDC) is a large class of structural proteins containing left-handed supercoiled structure. The clinical value and the functional implication of CCDC in colorectal cancer (CRC) remain unknown. Based on the genetic, transcriptional, and clinical data from The Cancer Genome Atlas, five of thirty-six CCDC proteins were differentially expressed in the CRC and associated with the survival of patients with CRC. A CCDC-score model was established to evaluate the prognosis of patients. The potential function of Coiled-Coil Domain-Containing 154 (CCDC154) was investigated using bioinformatical methods, which unveiled that high expression of CCDC154 indicates poor survival for patients with CRC and correlates with low infiltration of CD8 T cells and high infiltration of neutrophils, indicating that CCDC154 enhances tumor growth and metastasis. CCDC154 interacts with Minichromosome Maintenance Complex Component 2 (MCM2) protein and promotes malignant phenotype via MCM2. We validated the expression level and survival prediction value of CCDC154 in clinical samples, and analyzed its co-expression of MCM2, Ki-67 and p53. This work discloses the role of CCDC in clinical setting and CCDC154 functions in CRC.

摘要

卷曲螺旋结构域蛋白(CCDC)是一大类含有左手超螺旋结构的结构蛋白。CCDC 在结直肠癌(CRC)中的临床价值和功能意义尚不清楚。基于癌症基因组图谱(TCGA)的遗传、转录和临床数据,在 CRC 中,36 种 CCDC 蛋白中有 5 种表达差异,并与 CRC 患者的生存相关。建立了 CCDC 评分模型来评估患者的预后。使用生物信息学方法研究了卷曲螺旋结构域蛋白 154(CCDC154)的潜在功能,结果表明 CCDC154 的高表达预示着 CRC 患者的生存不良,并且与 CD8+T 细胞浸润减少和中性粒细胞浸润增加相关,这表明 CCDC154 促进了肿瘤的生长和转移。CCDC154 与微小染色体维持复合物成分 2(MCM2)蛋白相互作用,并通过 MCM2 促进恶性表型。我们在临床样本中验证了 CCDC154 的表达水平和生存预测价值,并分析了其与 MCM2、Ki-67 和 p53 的共表达。这项工作揭示了 CCDC 在临床环境中的作用以及 CCDC154 在 CRC 中的功能。

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