Department of Radiation Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210000, Jiangsu, China.
Department of Radiation Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210000, Jiangsu, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, 210000, Jiangsu, China.
Biochem Biophys Res Commun. 2021 Jun 11;557:192-198. doi: 10.1016/j.bbrc.2021.04.020. Epub 2021 Apr 16.
Kinesin family member 18A (KIF18A) is significantly overexpressed and is related to the poor prognosis of human cancers. However, the function of KIF18A in esophageal cancer (EC) is still unclear. Human EC cell lines were used in this study. KIF18A expression in human tissues was assessed using Gene Expression Profiling Interactive Analysis 2.0 (GEPIA2). The expressions of KIF18A or IGF2BP3 in EC cells were detected using qRT-PCR or WB. Cells were transfected using si-KIF18A, si-IGF2BP3, and plasmid IGF2BP3. The abilities of proliferation, migration, and invasion were detected by EdU, wound-healing, and transwell assay. The interaction between KIF18A and IGF2BP3 was predicted by starBase v3.0 and studied by RIP and RNA stability assay. Colony formation assay was used to reflect the changes of radiosensitivity in EC cells. KIF18A was upregulated in EC, and KIF18A knockdown inhibited EC cell proliferation, migration, invasion, and radioresistance. The prediction in starBase and RIP assay results showed that KIF18A mRNA could bind to IGF2BP3 protein in EC cells. RNA stability assay was performed to confirm that IGF2BP3 affects mRNA stability of KIF18A. Further studies also showed that IGF2BP3 could positively regulate KIF18A on proliferation, migration, invasion, and radioresistance. Our findings first revealed an oncogenic effect of KIF18A in human EC progression. KIF18A expression was associated with radioresistance of EC cells. The binding relationship between KIF18A and IGF2BP3 might influence the mRNA stability of KIF18A in EC cell lines.
驱动蛋白家族成员 18A（KIF18A）表达显著上调，与人类癌症的不良预后相关。然而，KIF18A 在食管癌（EC）中的功能仍不清楚。本研究使用人 EC 细胞系。使用基因表达谱分析交互式分析 2.0（GEPIA2）评估人组织中 KIF18A 的表达。使用 qRT-PCR 或 WB 检测 EC 细胞中 KIF18A 或 IGF2BP3 的表达。使用 si-KIF18A、si-IGF2BP3 和质粒 IGF2BP3 转染细胞。通过 EdU、划痕愈合和 Transwell 测定检测增殖、迁移和侵袭能力。通过 starBase v3.0 预测 KIF18A 和 IGF2BP3 之间的相互作用，并通过 RIP 和 RNA 稳定性测定研究。集落形成测定用于反映 EC 细胞放射敏感性的变化。KIF18A 在 EC 中上调，KIF18A 敲低抑制 EC 细胞增殖、迁移、侵袭和放射抗性。starBase 和 RIP 测定结果的预测表明，KIF18A mRNA 可在 EC 细胞中与 IGF2BP3 蛋白结合。进行 RNA 稳定性测定以确认 IGF2BP3 影响 KIF18A 的 mRNA 稳定性。进一步的研究还表明，IGF2BP3 可以正向调节 KIF18A 的增殖、迁移、侵袭和放射抗性。我们的研究结果首次揭示了 KIF18A 在人类 EC 进展中的致癌作用。KIF18A 的表达与 EC 细胞的放射抗性有关。KIF18A 和 IGF2BP3 之间的结合关系可能影响 EC 细胞系中 KIF18A 的 mRNA 稳定性。
