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Cell division cycle associated 8: A novel diagnostic and prognostic biomarker for hepatocellular carcinoma
The cell division cycle associated 8 (CDCA8) is a crucial component of the chromosome passenger complex (CPC). It has been implicated in the regulation of cell dynamic localization during mitosis. However, its role in hepatocellular carcinoma (HCC) is not clearly known. In this study, data of 374 pa...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650035/ https://www.ncbi.nlm.nih.gov/pubmed/34741389 http://dx.doi.org/10.1111/jcmm.17032 |
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author | Cui, Xiao‐Han Peng, Qiu‐Ju Li, Ren‐Zhi Lyu, Xia‐Jie Zhu, Chun‐Fu Qin, Xi‐Hu |
author_facet | Cui, Xiao‐Han Peng, Qiu‐Ju Li, Ren‐Zhi Lyu, Xia‐Jie Zhu, Chun‐Fu Qin, Xi‐Hu |
author_sort | Cui, Xiao‐Han |
collection | PubMed |
description | The cell division cycle associated 8 (CDCA8) is a crucial component of the chromosome passenger complex (CPC). It has been implicated in the regulation of cell dynamic localization during mitosis. However, its role in hepatocellular carcinoma (HCC) is not clearly known. In this study, data of 374 patients with HCC were retrieved from the Cancer Genome Atlas (TCGA) database. Pan analysis of Gene Expression Profiling Interactive Analysis (GEPIA) database was performed to profile the mRNA expression of CDCA8 in HCC. Then, the Kaplan‐Meier plotter database was analysed to determine the prognostic value of CDCA8 in HCC. In addition, samples of tumour and adjacent normal tissues were collected from 88 HCC patients to perform immunohistochemistry (IHC), reverse transcription‐quantitative polymerase chain reaction (qRT‐PCR) and Western blotting. The results obtained from bioinformatic analyses were validated through CCK‐8 assay, EdU assay, colony formation assay, cell cycle assays and Western blotting experiments. Analysis of the Kaplan‐Meier plotter database showed that high expression of CDCA8 may lead to poor overall survival (OS, p = 4.06e‐05) in patients with HCC. For the 88 patients with HCC, we found that stages and grades appeared to be strongly linked with CDCA8 expression. Furthermore, the high expression of CDCA8 was found to be correlated with poor OS (p = 0.0054) and progression‐free survival (PFS, p = 0.0009). In vitro experiments revealed that inhibition of CDCA8 slowed cell proliferation and blocked the cell cycle at the G0/G1 phase. In vivo experiments demonstrated that inhibition of CDCA8 inhibited tumour growth. Finally, blockade of CDCA8 reduced the expression levels of cyclin A2, cyclin D1, CDK4, CDK6, Ki67 and PCNA. And, there is an interaction between CDCA8 and E2F1. In conclusion, this research demonstrates that CDCA8 may serve as a biomarker for early diagnosis and prognosis prediction of HCC patients. In addition, CDCA8 could be an effective therapeutic target in HCC. |
format | Online Article Text |
id | pubmed-8650035 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86500352021-12-20 Cell division cycle associated 8: A novel diagnostic and prognostic biomarker for hepatocellular carcinoma Cui, Xiao‐Han Peng, Qiu‐Ju Li, Ren‐Zhi Lyu, Xia‐Jie Zhu, Chun‐Fu Qin, Xi‐Hu J Cell Mol Med Original Articles The cell division cycle associated 8 (CDCA8) is a crucial component of the chromosome passenger complex (CPC). It has been implicated in the regulation of cell dynamic localization during mitosis. However, its role in hepatocellular carcinoma (HCC) is not clearly known. In this study, data of 374 patients with HCC were retrieved from the Cancer Genome Atlas (TCGA) database. Pan analysis of Gene Expression Profiling Interactive Analysis (GEPIA) database was performed to profile the mRNA expression of CDCA8 in HCC. Then, the Kaplan‐Meier plotter database was analysed to determine the prognostic value of CDCA8 in HCC. In addition, samples of tumour and adjacent normal tissues were collected from 88 HCC patients to perform immunohistochemistry (IHC), reverse transcription‐quantitative polymerase chain reaction (qRT‐PCR) and Western blotting. The results obtained from bioinformatic analyses were validated through CCK‐8 assay, EdU assay, colony formation assay, cell cycle assays and Western blotting experiments. Analysis of the Kaplan‐Meier plotter database showed that high expression of CDCA8 may lead to poor overall survival (OS, p = 4.06e‐05) in patients with HCC. For the 88 patients with HCC, we found that stages and grades appeared to be strongly linked with CDCA8 expression. Furthermore, the high expression of CDCA8 was found to be correlated with poor OS (p = 0.0054) and progression‐free survival (PFS, p = 0.0009). In vitro experiments revealed that inhibition of CDCA8 slowed cell proliferation and blocked the cell cycle at the G0/G1 phase. In vivo experiments demonstrated that inhibition of CDCA8 inhibited tumour growth. Finally, blockade of CDCA8 reduced the expression levels of cyclin A2, cyclin D1, CDK4, CDK6, Ki67 and PCNA. And, there is an interaction between CDCA8 and E2F1. In conclusion, this research demonstrates that CDCA8 may serve as a biomarker for early diagnosis and prognosis prediction of HCC patients. In addition, CDCA8 could be an effective therapeutic target in HCC. John Wiley and Sons Inc. 2021-11-05 2021-12 /pmc/articles/PMC8650035/ /pubmed/34741389 http://dx.doi.org/10.1111/jcmm.17032 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Cui, Xiao‐Han Peng, Qiu‐Ju Li, Ren‐Zhi Lyu, Xia‐Jie Zhu, Chun‐Fu Qin, Xi‐Hu Cell division cycle associated 8: A novel diagnostic and prognostic biomarker for hepatocellular carcinoma |
title | Cell division cycle associated 8: A novel diagnostic and prognostic biomarker for hepatocellular carcinoma |
title_full | Cell division cycle associated 8: A novel diagnostic and prognostic biomarker for hepatocellular carcinoma |
title_fullStr | Cell division cycle associated 8: A novel diagnostic and prognostic biomarker for hepatocellular carcinoma |
title_full_unstemmed | Cell division cycle associated 8: A novel diagnostic and prognostic biomarker for hepatocellular carcinoma |
title_short | Cell division cycle associated 8: A novel diagnostic and prognostic biomarker for hepatocellular carcinoma |
title_sort | cell division cycle associated 8: a novel diagnostic and prognostic biomarker for hepatocellular carcinoma |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650035/ https://www.ncbi.nlm.nih.gov/pubmed/34741389 http://dx.doi.org/10.1111/jcmm.17032 |
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