1. Academic Validation
  2. Budding uninhibited by benzimidazoles 1 overexpression is associated with poor prognosis and malignant phenotype: A promising therapeutic target for lung adenocarcinoma

Budding uninhibited by benzimidazoles 1 overexpression is associated with poor prognosis and malignant phenotype: A promising therapeutic target for lung adenocarcinoma

  • Thorac Cancer. 2023 Feb 24. doi: 10.1111/1759-7714.14822.
Rui Chen 1 2 Zhiping Wang 3 Tianzhu Lu 2 Yuzhen Liu 1 2 Yulong Ji 2 Yilin Yu 3 Fangfang Tou 1 4 Shanxian Guo 1 2
Affiliations

Affiliations

  • 1 Graduate School, Medical College of Nanchang University, Nanchang, China.
  • 2 Jiangxi Key Laboratory of Translational Research for Cancer, Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, China.
  • 3 Fujian Medical University, Fuzhou, China.
  • 4 Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China.
Abstract

Background: The budding uninhibited by benzimidazoles (BUB) family is involved in the cell cycle process as mitotic checkpoint components. Abnormal proliferation is a vital process in the development of lung adenocarcinoma (LUAD). Nevertheless, the roles of BUB1 in LUAD remain unclear. In this study, we evaluated the prognostic value and biological functions of BUB1 in LUAD using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), clinical LUAD samples, and in vitro experiments.

Methods: The expression, prognostic significance, functions, immune infiltration, and methylation of BUB1 in LUAD were comprehensively analyzed using TCGA, GEO, Gene Expression Profiling Interactive Analysis, Metascape, cBioPortal, MethSurv, and cancerSEA databases. Furthermore, we performed a battery of in vitro experiments and immunohistochemistry (IHC) to verify the bioinformatics results.

Results: Multivariate analysis revealed that BUB1 overexpression was an independent prognostic factor (hazard ratio = 1.499, p = 0.013). Functional enrichment analysis showed that BUB1 was correlated with cell cycle, proliferation, DNA repair, DNA damage, and invasion (p < 0.05). Finally, in vitro experiments showed that downregulation of BUB1 inhibited the proliferation, migration, and invasion of LUAD cells and promoted LUAD cell Apoptosis. IHC also showed that BUB1 was overexpressed in LUAD (p < 0.001) and was significantly associated with poor prognosis (p < 0.001).

Conclusions: Our bioinformatics and IHC analyses revealed that BUB1 overexpression was an adverse prognostic factor in LUAD. In vitro experiments demonstrated that BUB1 promoted tumor cell proliferation, migration, and invasion in LUAD. These results indicated that BUB1 was a promising biomarker and potential therapeutic target in LUAD.

Keywords

budding uninhibited by benzimidazoles 1; cell cycle; immunohistochemistry; lung adenocarcinoma; methylation.

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