血小板素蛋白1(TSP1)以其在癌症进展中的细胞特异性功能而闻名，如增殖和迁移。它包含22个外显子，可能产生几种不同的转录本。在这里，我们在人类甲状腺癌细胞和组织中鉴定了TSP1V作为新的TSP1剪接变体，其由内含子保留(IR)产生。我们观察到，与TSP1野生型相比，TSP1V在体内和体外功能上抑制了肿瘤生成。这些TSP1V的活动是通过抑制磷酸化Smad和磷酸化焦点粘着激酶引起的。反转录聚合酶链反应和小基因实验揭示了一些植物化学物质/非甾体抗炎药物增强了IR。我们进一步发现RNA结合蛋白5(RBM5)抑制了由磺达奈治疗诱导的IR。此外，磺达奈还以时间为基础减少了磷酸化RBM5水平。此外，反式-查尔酮去甲基化了TSP1V，从而防止甲基-CpG结合蛋白2结合到TSP1V基因。此外，TSP1V水平在分化型甲状腺癌患者中显著低于良性甲状腺结节患者，表明其在肿瘤进展中的潜在应用作为诊断生物标志物。© 2023。作者授予Springer Nature Limited独家许可。

Thrombospondin 1 (TSP1) is known for its cell-specific functions in cancer progression, such as proliferation and migration. It contains 22 exons that may potentially produce several different transcripts. Here, we identified TSP1V as a novel TSP1-splicing variant produced by intron retention (IR) in human thyroid cancer cells and tissues. We observed that TSP1V functionally inhibited tumorigenesis contrary to TSP1 wild-type, as identified in vivo and in vitro. These activities of TSP1V are caused by inhibiting phospho-Smad and phospho-focal adhesion kinase. Reverse transcription polymerase chain reaction and minigene experiments revealed that some phytochemicals/non-steroidal anti-inflammatory drugs enhanced IR. We further found that RNA-binding motif protein 5 (RBM5) suppressed IR induced by sulindac sulfide treatment. Additionally, sulindac sulfide reduced phospho-RBM5 levels in a time-dependent manner. Furthermore, trans-chalcone demethylated TSP1V, thereby preventing methyl-CpG-binding protein 2 binding to TSP1V gene. In addition, TSP1V levels were significantly lower in patients with differentiated thyroid carcinoma than in those with benign thyroid nodule, indicating its potential application as a diagnostic biomarker in tumor progression.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.