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NudCD1 as a prognostic marker in colorectal cancer and its role in the upregulation of cellular spindle assembly checkpoint genes and LIS1 pathways

OBJECTIVE: To investigate the role of NudCD1 in spindle assembly checkpoint regulation and in the prognosis of colorectal cancer.  METHODS: Immunohistochemical staining was used to detect in situ expression of NudCD1 in 100 colorectal cancer tissue samples. A chi-square test was used to analyse the...

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Autores principales: Feng, Wen-Ming, Gong, Hui, Wang, Yong-Chun, Wang, Yao, Xue, Tao, Zhang, Ting, Cui, Ge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476325/
https://www.ncbi.nlm.nih.gov/pubmed/36104662
http://dx.doi.org/10.1186/s12885-022-10041-4
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author Feng, Wen-Ming
Gong, Hui
Wang, Yong-Chun
Wang, Yao
Xue, Tao
Zhang, Ting
Cui, Ge
author_facet Feng, Wen-Ming
Gong, Hui
Wang, Yong-Chun
Wang, Yao
Xue, Tao
Zhang, Ting
Cui, Ge
author_sort Feng, Wen-Ming
collection PubMed
description OBJECTIVE: To investigate the role of NudCD1 in spindle assembly checkpoint regulation and in the prognosis of colorectal cancer.  METHODS: Immunohistochemical staining was used to detect in situ expression of NudCD1 in 100 colorectal cancer tissue samples. A chi-square test was used to analyse the correlation between the NudCD1 protein expression level of the cancer tissues and clinicopathological features. The Kaplan–Meier survival analysis was used to assess the correlation between the NudCD1 mRNA expression and the three-year survival of patients with colorectal cancer. The impact of NudCD1 on the development of colorectal cancer and the underlying molecular mechanisms were assessed by flow cytometry cell cycle and apoptosis assays after lentiviral overexpression of NudCD1 in two colorectal cancer cell lines. Quantitative real-time PCR was used to assess mRNA expression of the cellular spindle assembly checkpoint genes BUB1, BUBR1, MAD1, CDC20 and MPS1, as well as the downstream genes LIS1, DYNC1H1, and DYNLL1 in the NudC/LIS1/dynein pathway. RESULTS: Compared with normal intestinal tissue (8.00% with high expression), the expression of NudCD1 protein in colorectal cancer tissue was significantly higher (58.00% with high expression, P < 0.01). In addition, expression of NudCD1 significantly correlated with the degree of tumour differentiation and the TNM staging (P < 0.01), as well as the depth of invasion of the primary tumour and lymph node metastasis (P < 0.05). However, there was no correlation with gender, age, tumour site, gross type, tumour size or distant metastasis. The Kaplan–Meier survival analysis showed that patients with high NudCD1 expression in colorectal cancer tissues had a significantly shorter survival time than those with low expression of NudCD1 (P < 0.01). Compared with the transfection of the empty vector, colon cancer HT-29 cells with overexpressed NudCD1 had significantly increased mRNA levels of BUBR1, MPS1 and LIS1. The DNA synthesis phase (S phase) was significantly shorter in cells overexpressing NudCD1 than in the control group (43.83% ± 1.57%, P < 0.05), while there was no difference in apoptosis in the two groups. CONCLUSION: NudCD1 can serve as a valuable prognostic marker for colorectal cancer. It may be involved in the regulation of spindle-assembly checkpoint-gene expression and the LIS1 pathway of colorectal cancer cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-10041-4.
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spelling pubmed-94763252022-09-16 NudCD1 as a prognostic marker in colorectal cancer and its role in the upregulation of cellular spindle assembly checkpoint genes and LIS1 pathways Feng, Wen-Ming Gong, Hui Wang, Yong-Chun Wang, Yao Xue, Tao Zhang, Ting Cui, Ge BMC Cancer Research OBJECTIVE: To investigate the role of NudCD1 in spindle assembly checkpoint regulation and in the prognosis of colorectal cancer.  METHODS: Immunohistochemical staining was used to detect in situ expression of NudCD1 in 100 colorectal cancer tissue samples. A chi-square test was used to analyse the correlation between the NudCD1 protein expression level of the cancer tissues and clinicopathological features. The Kaplan–Meier survival analysis was used to assess the correlation between the NudCD1 mRNA expression and the three-year survival of patients with colorectal cancer. The impact of NudCD1 on the development of colorectal cancer and the underlying molecular mechanisms were assessed by flow cytometry cell cycle and apoptosis assays after lentiviral overexpression of NudCD1 in two colorectal cancer cell lines. Quantitative real-time PCR was used to assess mRNA expression of the cellular spindle assembly checkpoint genes BUB1, BUBR1, MAD1, CDC20 and MPS1, as well as the downstream genes LIS1, DYNC1H1, and DYNLL1 in the NudC/LIS1/dynein pathway. RESULTS: Compared with normal intestinal tissue (8.00% with high expression), the expression of NudCD1 protein in colorectal cancer tissue was significantly higher (58.00% with high expression, P < 0.01). In addition, expression of NudCD1 significantly correlated with the degree of tumour differentiation and the TNM staging (P < 0.01), as well as the depth of invasion of the primary tumour and lymph node metastasis (P < 0.05). However, there was no correlation with gender, age, tumour site, gross type, tumour size or distant metastasis. The Kaplan–Meier survival analysis showed that patients with high NudCD1 expression in colorectal cancer tissues had a significantly shorter survival time than those with low expression of NudCD1 (P < 0.01). Compared with the transfection of the empty vector, colon cancer HT-29 cells with overexpressed NudCD1 had significantly increased mRNA levels of BUBR1, MPS1 and LIS1. The DNA synthesis phase (S phase) was significantly shorter in cells overexpressing NudCD1 than in the control group (43.83% ± 1.57%, P < 0.05), while there was no difference in apoptosis in the two groups. CONCLUSION: NudCD1 can serve as a valuable prognostic marker for colorectal cancer. It may be involved in the regulation of spindle-assembly checkpoint-gene expression and the LIS1 pathway of colorectal cancer cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-10041-4. BioMed Central 2022-09-14 /pmc/articles/PMC9476325/ /pubmed/36104662 http://dx.doi.org/10.1186/s12885-022-10041-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Feng, Wen-Ming
Gong, Hui
Wang, Yong-Chun
Wang, Yao
Xue, Tao
Zhang, Ting
Cui, Ge
NudCD1 as a prognostic marker in colorectal cancer and its role in the upregulation of cellular spindle assembly checkpoint genes and LIS1 pathways
title NudCD1 as a prognostic marker in colorectal cancer and its role in the upregulation of cellular spindle assembly checkpoint genes and LIS1 pathways
title_full NudCD1 as a prognostic marker in colorectal cancer and its role in the upregulation of cellular spindle assembly checkpoint genes and LIS1 pathways
title_fullStr NudCD1 as a prognostic marker in colorectal cancer and its role in the upregulation of cellular spindle assembly checkpoint genes and LIS1 pathways
title_full_unstemmed NudCD1 as a prognostic marker in colorectal cancer and its role in the upregulation of cellular spindle assembly checkpoint genes and LIS1 pathways
title_short NudCD1 as a prognostic marker in colorectal cancer and its role in the upregulation of cellular spindle assembly checkpoint genes and LIS1 pathways
title_sort nudcd1 as a prognostic marker in colorectal cancer and its role in the upregulation of cellular spindle assembly checkpoint genes and lis1 pathways
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476325/
https://www.ncbi.nlm.nih.gov/pubmed/36104662
http://dx.doi.org/10.1186/s12885-022-10041-4
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