Cancer-Specifically Re-Spliced TSG101 mRNA Promotes Invasion and Metastasis of Nasopharyngeal Carcinoma
Cancer-Specifically Re-Spliced TSG101 mRNA Promotes Invasion and Metastasis of Nasopharyngeal Carcinoma
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DOI：
10.3390/ijms20030773
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发表时间：
2019-02-01
影响因子：
5.6
通讯作者：
Yeh, Te-Huei
中科院分区：
文献类型：
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作者：
Chua, Huey-Huey;Kameyama, Toshiki;Yeh, Te-Huei
TSG 101基因及其异常剪接的亚型TSG 101154 -1054与多种癌症的发生密切相关。异常TSG 101154 -1054 mRNA是由成熟TSG 101 mRNA的癌症特异性再剪接产生的。TSG 101154 -1054蛋白保护全长TSG 101蛋白免受泛素介导的降解，这表明TSG 101154 -1054蛋白参与了癌症的进展。在这里，我们证实了TSG 101154 -1054 mRNA的存在确实导致了TSG 101蛋白在人鼻咽癌（NPC）活检组织中的积累，这在NPC细胞系TW 01中的TSG 101154 -1054过表达中得到了重现。我们通过划痕愈合和transwell侵袭试验证明了TSG 101154 -1054蛋白在人类NPC恶性肿瘤中的潜在功能。通过增加TSG 101蛋白的稳定性，TSG 101154 -1054特异性增强TSG 101介导的TW 01细胞迁移和侵袭，表明其参与了体内NPC转移。这一发现揭示了TSG 101154 -1054通过TSG 101 mRNA的重新剪接在NPC转移中产生的功能意义，并暗示了其作为治疗靶点的潜在重要性。
TSG101 (Tumor susceptibility 101) gene and its aberrantly spliced isoform, termed TSG101154-1054, are tightly linked to tumorigenesis in various cancers. The aberrant TSG101154-1054 mRNA is generated from cancer-specific re-splicing of mature TSG101 mRNA. The TSG101154-1054 protein protects the full-length TSG101 protein from ubiquitin-mediated degradation, implicating TSG101154-1054 protein in the progression of cancer. Here, we confirmed that the presence of TSG101154-1054 mRNA indeed caused an accumulation of the TSG101 protein in biopsies of human nasopharyngeal carcinoma (NPC), which was recapitulated by the overexpression of TSG101154-1054 in the NPC cell line TW01. We demonstrate the potential function of the TSG101154-1054 protein in the malignancy of human NPC with scratch-wound healing and transwell invasion assays. By increasing the stability of the TSG101 protein, TSG101154-1054 specifically enhanced TSG101-mediated TW01 cell migration and invasion, suggesting the involvement in NPC metastasis in vivo. This finding sheds light on the functional significance of TSG101154-1054 generation via re-splicing of TSG101 mRNA in NPC metastasis and hints at its potential importance as a therapeutic target.