肿瘤特异性重剪的 TSG101 mRNA 促进鼻咽癌的侵袭和转移。
Cancer-Specifically Re-Spliced TSG101 mRNA Promotes Invasion and Metastasis of Nasopharyngeal Carcinoma.
机构信息
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.
出版信息
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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