KIF15 promotes the evolution of gastric cancer cells through inhibition of reactive oxygen species-mediated apoptosis
KIF15 promotes the evolution of gastric cancer cells through inhibition of reactive oxygen species-mediated apoptosis
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DOI：
10.1002/jcp.29743
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发表时间：
2020-04-27
影响因子：
5.6
通讯作者：
Zhang，Weijie
中科院分区：
文献类型：
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作者：
Tao，Jinqiu;Sun，Guangli;Zhang，Weijie
驱动蛋白家族成员15（Kinesin family member 15，KIF 15）是驱动蛋白超家族的一员，它促进细胞有丝分裂，参与细胞内物质的转运，并帮助结构组装和细胞信号转导通路。然而，其在胃癌（GC）发展中的生物学作用和分子作用机制仍不清楚。在本研究中，对癌症基因组图谱（TCGA）、基因表达综合数据库和Kaplan-Meier曲线数据库进行综合分析，以预测KIF 15在GC患者中的表达和预后价值。通过定量聚合酶链反应检测KIF 15在GC细胞和组织中的表达。通过体外细胞增殖、存活率、集落形成能力和流式细胞术测定以及体内致瘤性测定来评估KIF 15敲低对GC细胞表型的影响。研究表明，KIF 15信使RNA在GC组织中的表达明显高于邻近组织，并且与肿瘤尺寸较大和患者预后不良密切相关。此外，功能研究表明，由于活性氧（ROS）产生的增加，干扰KIF 15的表达不仅降低细胞增殖，而且增加细胞凋亡和诱导细胞周期阻滞。ROS介导的c-Jun N-末端激酶/c-Jun信号传导的激活通过调节GC细胞周期和增加凋亡来降低细胞增殖。综上所述，本研究的结果表明，KIF 15是一种有助于GC进展的癌蛋白，并有望帮助确定GC中的新生物标志物和治疗靶点。
Kinesin family member 15 (KIF15) is a member of the kinesin superfamily of proteins, which promotes cell mitosis, participates in the transport of intracellular materials, and helps structural assembly and cell signaling pathways transduction. However, its biological role and molecular mechanisms of action in the development of gastric cancer (GC) remain unclear. In the present study, an integrated analysis of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus database, and Kaplan–Meier plotter database was performed to predict the expression and prognostic value of KIF15 in GC patients. Detection of KIF15 expression in GC cells and tissues was performed by a quantitative polymerase chain reaction. In vitro cell proliferation, viability, colony formation ability and flow cytometry assays, and in vivo tumorigenicity assay, were performed to evaluate the effects of KIF15 knockdown on GC cell phenotype. It was demonstrated that the expression of KIF15 messenger RNA in GC tissues was significantly higher compared with that in adjacent tissues, and was closely associated with larger tumor size and poor patient prognosis. In addition, functional studies demonstrated that, due to the increase in reactive oxygen species (ROS) generation, the interference with the expression of KIF15 not only decreased cell proliferation but also increased cell apoptosis and induced cell cycle arrest. ROS‐mediated activation of c‐Jun N‐terminal kinase/c‐Jun signaling reduced cell proliferation by regulating the GC cell cycle and increasing apoptosis. Taken together, the results of the present study indicate that KIF15 is an oncoprotein contributing to GC progression, and is expected to help identify novel biomarkers and treatment targets in GC.