Cancer Biomark. 2024;41(2):165-178. doi: 10.3233/CBM-240074.
Cervical cancer is a prevalent malignancy that significantly contributes to morbidity and mortality rates among women in developing nations. Although the association of KIF18A with various cancers has been established, its role in cervical squamous cell carcinoma (CESC) remains elusive.
The KIF18A impact on the progression of CESC and its underlying mechanism were investigated through comprehensive bioinformatics analysis utilizing publicly available datasets. The levels of KIF18A and CENPE were assessed in clinical CESC samples through western blotting and qRT-PCR. To discover the role and molecular pathways of KIF18A in CESC, a combination of experimental approaches, including wound-healing, flow cytometry, CCK-8, and Transwell assay, were employed.
Our results demonstrate a significant KIF18A expression upregulation in CESC tissues in contrast to healthy tissues. In vitro, KIF18A upregulation was found to enhance cell growth, migration, and invasion and activate the PI3K/AKT signaling pathway while concurrently suppressing apoptosis. Conversely, downregulating KIF18A exhibited contrasting effects. Mechanistically, we observed a positive significant connection between KIF18A and CENPE in CESC cells.
KIF18A promotes tumor growth in CESC by modulating the PI3K/AKT signaling pathway through regulation of CENPE, making it a potential biomarker for diagnosis and prognosis as well as a therapeutic target.
宫颈癌是一种常见的恶性肿瘤，在发展中国家的女性发病率和死亡率中占很大比例。虽然已经证实 KIF18A 与多种癌症有关，但它在宫颈鳞状细胞癌（CESC）中的作用仍不清楚。
通过利用公开数据集进行全面的生物信息学分析，研究了 KIF18A 对 CESC 进展的影响及其潜在机制。通过 Western blot 和 qRT-PCR 评估了临床 CESC 样本中 KIF18A 和 CENPE 的水平。为了发现 KIF18A 在 CESC 中的作用和分子途径，采用了包括划痕愈合、流式细胞术、CCK-8 和 Transwell 测定在内的实验方法组合。
我们的结果表明，与健康组织相比，CESC 组织中 KIF18A 的表达显著上调。在体外，发现上调 KIF18A 可增强细胞生长、迁移和侵袭，并激活 PI3K/AKT 信号通路，同时抑制细胞凋亡。相反，下调 KIF18A 则表现出相反的效果。在机制上，我们观察到 CESC 细胞中 KIF18A 与 CENPE 之间存在正相关关系。
KIF18A 通过调节 CENPE 来调节 PI3K/AKT 信号通路，从而促进 CESC 中的肿瘤生长，使其成为诊断、预后的潜在生物标志物以及治疗靶点。
