Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
Division of Gene Expression Mechanism, Institute for Comprehensive Medical Science, Fujita Health University, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
Int J Mol Sci. 2019 Feb 12;20(3):773. doi: 10.3390/ijms20030773.
(Tumor susceptibility 101) gene and its aberrantly spliced isoform, termed TSG101∆154-1054, are tightly linked to tumorigenesis in various cancers. The aberrant TSG101∆154-1054 mRNA is generated from cancer-specific re-splicing of mature TSG101 mRNA. The TSG101∆154-1054 protein protects the full-length TSG101 protein from ubiquitin-mediated degradation, implicating TSG101∆154-1054 protein in the progression of cancer. Here, we confirmed that the presence of TSG101∆154-1054 mRNA indeed caused an accumulation of the TSG101 protein in biopsies of human nasopharyngeal carcinoma (NPC), which was recapitulated by the overexpression of TSG101∆154-1054 in the NPC cell line TW01. We demonstrate the potential function of the TSG101∆154-1054 protein in the malignancy of human NPC with scratch-wound healing and transwell invasion assays. By increasing the stability of the TSG101 protein, TSG101∆154-1054 specifically enhanced TSG101-mediated TW01 cell migration and invasion, suggesting the involvement in NPC metastasis . This finding sheds light on the functional significance of TSG101∆154-1054 generation re-splicing of TSG101 mRNA in NPC metastasis and hints at its potential importance as a therapeutic target.
（肿瘤易感性 101）基因及其异常剪接的异构体，称为 TSG101∆154-1054，与各种癌症的肿瘤发生密切相关。异常的 TSG101∆154-1054 mRNA 是由成熟 TSG101 mRNA 的癌症特异性重新剪接产生的。TSG101∆154-1054 蛋白保护全长 TSG101 蛋白免受泛素介导的降解，暗示 TSG101∆154-1054 蛋白参与了癌症的进展。在这里，我们证实了 TSG101∆154-1054 mRNA 的存在确实导致了人鼻咽癌（NPC）活检中 TSG101 蛋白的积累，这可以通过 NPC 细胞系 TW01 中 TSG101∆154-1054 的过表达来重现。我们通过划痕愈合和 Transwell 侵袭实验证明了 TSG101∆154-1054 蛋白在人 NPC 恶性肿瘤中的潜在功能。通过增加 TSG101 蛋白的稳定性，TSG101∆154-1054 特异性增强了 TSG101 介导的 TW01 细胞迁移和侵袭，提示其参与 NPC 转移。这一发现揭示了 TSG101 mRNA 重新剪接产生 TSG101∆154-1054 在 NPC 转移中的功能意义，并暗示其作为治疗靶点的潜在重要性。
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