J Cancer 2022; 13(7):2336-2351. doi:10.7150/jca.68408 This issue
Department of Thyroid Surgery, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou 310009, Zhejiang, China.
Objective: This study aimed to clarify the function and potential mechanism of BUB1B in THCA.
Methods: 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.
Results: 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.
Conclusions: Present study identified BUB1B as a promising clinical prognostic factor in THCA, as well as a potential novel therapeutic target for cancer treatment.
Keywords: thyroid carcinoma, BUB1B, high expression, prognosis, mechanism