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BUB1B promotes hepatocellular carcinoma progression via activation of the mTORC1 signaling pathway
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) remai...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643650/ https://www.ncbi.nlm.nih.gov/pubmed/32977361 http://dx.doi.org/10.1002/cam4.3411 |
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author | Qiu, Jiannan Zhang, Shaopeng Wang, Peng Wang, Hao Sha, Bowen Peng, Hao Ju, Zheng Rao, Jianhua Lu, Ling |
author_facet | Qiu, Jiannan Zhang, Shaopeng Wang, Peng Wang, Hao Sha, Bowen Peng, Hao Ju, Zheng Rao, Jianhua Lu, Ling |
author_sort | Qiu, Jiannan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7643650 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-76436502020-11-13 BUB1B promotes hepatocellular carcinoma progression via activation of the mTORC1 signaling pathway Qiu, Jiannan Zhang, Shaopeng Wang, Peng Wang, Hao Sha, Bowen Peng, Hao Ju, Zheng Rao, Jianhua Lu, Ling Cancer Med Cancer Biology 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. John Wiley and Sons Inc. 2020-09-25 /pmc/articles/PMC7643650/ /pubmed/32977361 http://dx.doi.org/10.1002/cam4.3411 Text en © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Cancer Biology Qiu, Jiannan Zhang, Shaopeng Wang, Peng Wang, Hao Sha, Bowen Peng, Hao Ju, Zheng Rao, Jianhua Lu, Ling BUB1B promotes hepatocellular carcinoma progression via activation of the mTORC1 signaling pathway |
title | BUB1B promotes hepatocellular carcinoma progression via activation of the mTORC1 signaling pathway |
title_full | BUB1B promotes hepatocellular carcinoma progression via activation of the mTORC1 signaling pathway |
title_fullStr | BUB1B promotes hepatocellular carcinoma progression via activation of the mTORC1 signaling pathway |
title_full_unstemmed | BUB1B promotes hepatocellular carcinoma progression via activation of the mTORC1 signaling pathway |
title_short | BUB1B promotes hepatocellular carcinoma progression via activation of the mTORC1 signaling pathway |
title_sort | bub1b promotes hepatocellular carcinoma progression via activation of the mtorc1 signaling pathway |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643650/ https://www.ncbi.nlm.nih.gov/pubmed/32977361 http://dx.doi.org/10.1002/cam4.3411 |
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