Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, People's Republic of China.
Department of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, People's Republic of China.
Environ Toxicol. 2023 Sep;38(9):2047-2056. doi: 10.1002/tox.23812. Epub 2023 May 10.
Papillary thyroid carcinoma (PTC) is one of the most widespread malignant tumors of the endocrine system, with a high incidence. Budding uninhibited by benzimidazoles 1 (BUB1), one of the spindle assembly checkpoint (SAC) genes, is a multitask protein kinase required for eukaryotic chromosome segregation. Although BUB1 has been explored in several types of cancer, its biological role and molecular mechanisms in PTC remain unclear.
In this study, we performed an examination of four public datasets along with local PTC cohorts and discovered that BUB1 was elevated in PTC compared to non-cancer tissues. High BUB1 expression was linked with the status of BRAF , RAS, and TERT after statistical analysis.
Clinically, BUB1 is associated with a variety of clinicopathological features in PTC patients. Interestingly, analysis of the TCGA database showed that BUB1 was closely associated with poor prognosis of PTC and significantly correlated with PFS. As determined by regression analysis, BUB1, and T stage were independent predictors of PTC and were related to BRAF and lymph node metastatic status. By RT-qPCR, BUB1 was considerably overexpressed in PTC cell lines in comparison with normal thyroid epithelial cells.
We confirmed that the knockdown of BUB1 in BCPAP and TPC1 cell lines significantly inhibited cell proliferation, cloning, and migration in vitro experiments. These results imply that BUB1 may be a significant oncogenic gene that is directly associated with the prognosis of PTC and may represent a future target for therapeutic intervention.
甲状腺乳头状癌(PTC)是内分泌系统最常见的恶性肿瘤之一,发病率较高。Budding uninhibited by benzimidazoles 1(BUB1)是纺锤体组装检查点(SAC)基因之一,是真核细胞染色体分离所必需的多功能蛋白激酶。尽管 BUB1 在多种类型的癌症中得到了研究,但它在 PTC 中的生物学作用和分子机制仍不清楚。
本研究通过对四个公共数据集和本地 PTC 队列进行检查,发现与非癌组织相比,BUB1 在 PTC 中升高。统计学分析显示,BUB1 高表达与 BRAF、RAS 和 TERT 的状态有关。
临床上,BUB1 与 PTC 患者的多种临床病理特征有关。有趣的是,TCGA 数据库的分析表明,BUB1 与 PTC 的预后密切相关,与 PFS 显著相关。回归分析表明,BUB1 和 T 分期是 PTC 的独立预测因子,与 BRAF 和淋巴结转移状态有关。与正常甲状腺上皮细胞相比,BUB1 在 PTC 细胞系中的表达明显上调。
我们证实,在 BCPAP 和 TPC1 细胞系中敲低 BUB1 显著抑制了体外实验中的细胞增殖、克隆和迁移。这些结果表明,BUB1 可能是一个重要的致癌基因,与 PTC 的预后直接相关,可能成为未来治疗干预的靶点。