Yan Hai-Chao, Xiang Cheng
Department of Thyroid Surgery, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou 310009, Zhejiang, China.
J Cancer. 2022 Apr 18;13(7):2336-2351. doi: 10.7150/jca.68408. eCollection 2022.
This study aimed to clarify the function and potential mechanism of BUB1B in THCA. Expression of BUB1B in THCA was firstly determined, and its important prognostic value was then demonstrated. The potential mechanism was initially predicted by KEGG analysis. To explore the specific function of BUB1B in THCA, we used lentivirus infection to knock down the BUB1B, and then performed flow cytometry, colony formation, transwell, and wound-healing assays. Related protein expression was detected through western blotting. Additionally, we predicted the BUB1B-regulated pathways involved in THCA by GSEA analysis. BUB1B expression was highly increased in THCA tissues relative to normal controls. We further found that BUB1B was essential for tumor cell proliferation, and BUB1B high expression predicted a shorter PFS time of THCA patients. More importantly, Cox regression determined the BUB1B as an independent prognostic factor for PFS in THCA. BUB1B was initially found to participate in the cell cycle pathway from KEGG analysis. Unexpectedly, we did not detect the disturbing effect on the cell cycle distribution of THCA cells with BUB1B knockdown. But, BUB1B knockdown inhibited the proliferation, invasion, and migration of THCA cells, as well as increased apoptotic cells, and the results were further confirmed by western blotting. Through GSEA analysis, we predicted a positive correlation between BUB1B and metastasis-related pathways such as mTOR and NF-kappa B signaling pathways. Present study identified BUB1B as a promising clinical prognostic factor in THCA, as well as a potential novel therapeutic target for cancer treatment.
本研究旨在阐明BUB1B在甲状腺癌（THCA）中的功能及潜在机制。首先测定了BUB1B在THCA中的表达，随后证明了其重要的预后价值。通过KEGG分析初步预测了潜在机制。为了探究BUB1B在THCA中的具体功能，我们利用慢病毒感染敲低BUB1B，然后进行流式细胞术、集落形成、Transwell和伤口愈合实验。通过蛋白质免疫印迹法检测相关蛋白表达。此外，我们通过基因集富集分析（GSEA）预测了THCA中BUB1B调控的信号通路。与正常对照相比，THCA组织中BUB1B表达显著升高。我们进一步发现BUB1B对肿瘤细胞增殖至关重要，且BUB1B高表达预示THCA患者的无进展生存期（PFS）较短。更重要的是，Cox回归分析确定BUB1B是THCA患者PFS的独立预后因素。KEGG分析初步发现BUB1B参与细胞周期通路。出乎意料的是，我们未检测到敲低BUB1B对THCA细胞周期分布的干扰作用。但是，敲低BUB1B抑制了THCA细胞的增殖、侵袭和迁移，同时增加了凋亡细胞，蛋白质免疫印迹法进一步证实了这些结果。通过GSEA分析，我们预测BUB1B与mTOR和NF-κB信号通路等转移相关信号通路呈正相关。本研究确定BUB1B是THCA中一个有前景的临床预后因素，也是癌症治疗中一个潜在的新型治疗靶点。
