Department of Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China.
Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China.
Oxid Med Cell Longev. 2022 Dec 22;2022:1361135. doi: 10.1155/2022/1361135. eCollection 2022.
Dysregulation of eukaryotic translation initiation factor 1A, X-linked (), has been implicated in the pathogenesis of some cancers. However, the role of in endometrial carcinoma (EC) remains unknown. We investigated the expression in EC patients and assessed its tumorigenesis-associated function and nucleocytoplasmic transport mechanism and . The results indicated that the cytoplasmic EIF1AX expression showed a gradual increase when going from endometrium normal tissue, simple endometrial hyperplasia, complex endometrial hyperplasia, and endometrial atypical hyperplasia to EC, while vice versa for the nuclear EIF1AX expression. In addition, the cytoplasmic EIF1AX expression was positively correlated with histologic type, high International Federation of Gynecology and Obstetrics (FIGO) grade, advanced FIGO stage, deeper infiltration, high Ki67 index, and shorter recurrence-free survival in EC patients. , short hairpin RNA-mediated depletion or SV40NLS-mediated EIF1AX import into the nucleus in multiple human EC cells potently suppressed cell migration and invasion, epithelial-mesenchymal transition, and lung metastasis. Moreover, exportin 1 induced the transport of EIF1AX from the nucleus to the cytoplasm that could be inhibited by leptomycin B treatment or the mutation in the location sequence. These results demonstrate that cytoplasmic EIF1AX may play a key role in the incidence and promotion of EC, and thus, targeting EIF1AX or its nucleocytoplasmic transport process may offer an effective new therapeutic approach to EC.
X 连锁真核翻译起始因子 1A 调控因子（）失调与一些癌症的发病机制有关。然而，在子宫内膜癌（EC）中，的作用尚不清楚。我们研究了 EC 患者中的表达情况，并评估了其与肿瘤发生相关的功能和核质转运机制。结果表明，从正常子宫内膜组织、单纯性子宫内膜增生、复杂性子宫内膜增生和子宫内膜不典型增生到 EC，细胞质 EIF1AX 表达逐渐增加，而核内 EIF1AX 表达则相反。此外，细胞质 EIF1AX 表达与组织学类型、国际妇产科联合会（FIGO）分级高、FIGO 分期晚期、浸润更深、Ki67 指数高和 EC 患者无复发生存期缩短呈正相关。短发夹 RNA 介导的耗竭或 SV40NLS 介导的 EIF1AX 导入多种人 EC 细胞中，可显著抑制细胞迁移和侵袭、上皮间质转化和肺转移。此外，输出蛋白 1 诱导 EIF1AX 从核内向细胞质的转运，该转运可被莱普霉素 B 处理或位置序列突变所抑制。这些结果表明，细胞质 EIF1AX 可能在 EC 的发生和促进中起关键作用，因此，靶向 EIF1AX 或其核质转运过程可能为 EC 提供一种有效的新治疗方法。
