Overexpression of KIF18A promotes cell proliferation, inhibits apoptosis, and independently predicts unfavorable prognosis in lung adenocarcinoma
Overexpression of KIF18A promotes cell proliferation, inhibits apoptosis, and independently predicts unfavorable prognosis in lung adenocarcinoma
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KIF18A 的过度表达可促进细胞增殖、抑制细胞凋亡，并独立预测肺腺癌的不良预后。
DOI：
10.1002/iub.2030
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发表时间：
2019-07-01
期刊：
影响因子：
4.6
通讯作者：
Li, Zongrong
中科院分区：
文献类型：
--
作者：
Zhong, Yonglong;Jiang, Lingyu;Li, Zongrong
激酶蛋白家族成员18A （KIF18A）作为激酶蛋白超家族成员，在多种人类癌症中显著过表达和功能异常。但其在肺腺癌（LUAD）中的表达谱尚不清楚。在本工作中，我们利用来自癌症基因组图谱（TCGA）的数据，评估了KIF18A在LUAD中的表达模式和预后价值。此外，我们还分析了其基因失调的潜在机制。实验和生物信息学分析结果表明，与正常组织相比，KIF18A在LUAD组织中的表达显著增加。此外，KIF18A高表达的患者总生存期（OS）和无复发生存期（RFS）明显较差。单因素和多因素分析表明，KIF18A表达升高与不良的OS和RFS独立相关。此外，通过分析TCGA-LUAD的深度测序数据，我们发现在2.6%的LUAD病例中检测到KIF18A突变，并且KIF18A表达升高与基因扩增而非DNA甲基化有关。此外，基因共表达网络分析显示，共检测到339个KIF18A共表达基因，并在几种肿瘤相关通路中富集，尤其是细胞周期。在体外和体内，敲低KIF18A可显著抑制细胞增殖。此外，沉默KIF18A可诱导LUAD细胞凋亡，使细胞周期停留在G2/M期。KIF18A促进细胞增殖，抑制细胞凋亡，是LUAD患者有价值的预后预测因子和潜在的治疗靶点。(c) 2019 IUBMB Life, 2019
Kinesin family member 18A (KIF18A), as a member of the kinesin superfamily, is significantly overexpressed and abnormally functions in various human cancers. But, its expression profiling in the lung adenocarcinoma (LUAD) remains unclear. In the present work, using the data derived from the Cancer Genome Atlas (TCGA), we assessed the expression pattern and prognostic value of KIF18A in LUAD. In addition, we analyzed the underlying mechanism of its gene dysregulation. Experimental and bioinformatic analysis results showed that KIF18A expression was dramatically increased in LUAD tissues compared with the normal counterparts. Moreover, the patients with high KIF18A expression had significantly poorer overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate analyses indicated that increased KIF18A expression was independently associated with unfavorable OS and RFS. In addition, by analyzing deep sequencing data from TCGA-LUAD, we found that KIF18A mutation was detected in 2.6% of LUAD cases, and increased KIF18A expression was associated with genetic amplification rather than DNA methylation. Moreover, gene co-expression network analysis revealed that a total of 339 KIF18A co-expressed genes were detected and enriched in several tumor-related pathways, especially cell cycle. Knockdown of KIF18A significantly inhibited cell proliferation in vitro and in vivo. Furthermore, silencing KIF18A induced LUAD cells apoptosis and arrested the cell cycle in the G2/M phase. KIF18A promotes cell proliferation, inhibits apoptosis, and is a valuable prognostic predictor and potential therapeutic target for the patients with LUAD. (c) 2019 IUBMB Life, 2019