Open AccessBUB1B promotes hepatocellular carcinoma progression via activation of the mTORC1 signaling pathway
Author(s) -
Qiu Jiannan,
Zhang Shaopeng,
Wang Peng,
Wang Hao,
Sha Bowen,
Peng Hao,
Ju Zheng,
Rao Jianhua,
Lu Ling
Publication year - 2020
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.3411
Subject(s) - bub1 , cancer research , mtorc1 , blot , cell growth , hepatocellular carcinoma , biology , flow cytometry , metastasis , signal transduction , downregulation and upregulation , mitosis , immunohistochemistry , medicine , cancer , pi3k/akt/mtor pathway , microbiology and biotechnology , immunology , gene , genetics , kinetochore , chromosome
Abstract Background and Aims Accumulating studies identified that BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) is integrally involved in the initiation and development of tumors. Nevertheless, the precise biological role and underlying mechanisms of BUB1B in hepatocellular carcinoma (HCC) remain indistinct. Method To figure out the role of BUB1B in HCC, we first assessed its expression using The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. We then verified BUB1B expression in HCC tissues, nontumor tissues, and HCC cell lines through western blotting, quantitative reverse transcription‐polymerase chain reaction, and immunohistochemistry. To explore the specific function of BUB1B in HCC in vivo and in vitro, we performed the flow cytometry, Cell Counting Kit‐8, 5‐ethynyl‐2′‐deoxyuridine incorporation, colony formation, Transwell, wound‐healing, subcutaneous tumor growth, and metastasis assays. Additionally, we identified the BUB1B‐regulated pathways involved in HCC by using gene set enrichment analysis. Results Our data displayed that higher BUB1B expression was detected in HCC tissues and HCC cell lines. The overexpression of BUB1B was positively correlated with adverse clinicopathological characteristics. Survival analyses showed that lower recurrence‐free and overall survival rates were correlated with the overexpression of BUB1B in patients with HCC. Moreover, the malignancy of HCC was facilitated by BUB1B both in vivo and in vitro. Lastly, the results were confirmed by western blots, which showed that BUB1B upregulated mTORC1 signaling pathway in HCC. Meanwhile, the oncogenic effect of BUB1B will be impaired when the mTORC1 signaling pathway was inhibited by rapamycin. Conclusion We highlighted that BUB1B played an oncogenic role in HCC and was identified as a possible clinical prognostic factor and a potential novel therapeutic target for HCC.