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Vitamin D receptor prevents tumour development by regulating the Wnt/β-catenin signalling pathway in human colorectal cancer

BACKGROUND: Colorectal cancer (CRC) is a common disease threatening human lives worldwide, and vitamin D receptor (VDR) contributes protective roles in this disease. However, the molecular mechanisms underlying VDR protection in CRC progression require further investigation. METHODS: In this study,...

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Autores principales: Yu, Jie, Sun, Qi, Hui, Yi, Xu, Jinping, Shi, Pancheng, Chen, Yu, Chen, Yunzhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091620/
https://www.ncbi.nlm.nih.gov/pubmed/37046222
http://dx.doi.org/10.1186/s12885-023-10690-z
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author Yu, Jie
Sun, Qi
Hui, Yi
Xu, Jinping
Shi, Pancheng
Chen, Yu
Chen, Yunzhao
author_facet Yu, Jie
Sun, Qi
Hui, Yi
Xu, Jinping
Shi, Pancheng
Chen, Yu
Chen, Yunzhao
author_sort Yu, Jie
collection PubMed
description BACKGROUND: Colorectal cancer (CRC) is a common disease threatening human lives worldwide, and vitamin D receptor (VDR) contributes protective roles in this disease. However, the molecular mechanisms underlying VDR protection in CRC progression require further investigation. METHODS: In this study, we statistically analyzed the relationship between VDR expression and CRC development in patients and detected invasion and apoptosis in CRC cells with VDR overexpression and interference. We also detected the expression of key genes involved in Wnt/β-catenin signalling (β-catenin, lymphoid enhancer factor (LEF)-1 and cyclin D1) in SW480 cells and nude mice injected with VDR-overexpressing SW480 cells and observed tumour development. Additionally, we performed Co-immunoprecipitation (Co-IP) and glutathione-S-transferase (GST) pull-down assays to identify the protein interactions of VDR with β-catenin, dual luciferase (LUC) and chromatin immunoprecipitation (ChIP) to detect the activation of LEF-1 by VDR. RESULTS: The VDR level was closely related to the development and prognosis of CRC patients. VDR overexpression inhibited invasion but promoted apoptosis in cancer cells. β-catenin shRNA contributed oppositely to cancer cell activity with VDR shRNA. Additionally, VDR interacted with β-catenin at the protein level and blocked its nuclear accumulation. VDR regulated the expression of β-catenin, cyclin D1 and LEF-1 and directly activated LEF-1 transcription in vitro. Furthermore, nude mice injected with VDR-overexpressing SW480 cells revealed suppression of tumour growth and decreased expression of β-catenin, cyclin D1 and LEF-1. CONCLUSIONS: This study indicated that VDR protected against CRC disease in humans by inhibiting Wnt/β-catenin signalling to control cancer cell invasion and apoptosis, providing new evidence to explore VDR biomarkers or agonists for CRC patient diagnosis and treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10690-z.
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spelling pubmed-100916202023-04-13 Vitamin D receptor prevents tumour development by regulating the Wnt/β-catenin signalling pathway in human colorectal cancer Yu, Jie Sun, Qi Hui, Yi Xu, Jinping Shi, Pancheng Chen, Yu Chen, Yunzhao BMC Cancer Research BACKGROUND: Colorectal cancer (CRC) is a common disease threatening human lives worldwide, and vitamin D receptor (VDR) contributes protective roles in this disease. However, the molecular mechanisms underlying VDR protection in CRC progression require further investigation. METHODS: In this study, we statistically analyzed the relationship between VDR expression and CRC development in patients and detected invasion and apoptosis in CRC cells with VDR overexpression and interference. We also detected the expression of key genes involved in Wnt/β-catenin signalling (β-catenin, lymphoid enhancer factor (LEF)-1 and cyclin D1) in SW480 cells and nude mice injected with VDR-overexpressing SW480 cells and observed tumour development. Additionally, we performed Co-immunoprecipitation (Co-IP) and glutathione-S-transferase (GST) pull-down assays to identify the protein interactions of VDR with β-catenin, dual luciferase (LUC) and chromatin immunoprecipitation (ChIP) to detect the activation of LEF-1 by VDR. RESULTS: The VDR level was closely related to the development and prognosis of CRC patients. VDR overexpression inhibited invasion but promoted apoptosis in cancer cells. β-catenin shRNA contributed oppositely to cancer cell activity with VDR shRNA. Additionally, VDR interacted with β-catenin at the protein level and blocked its nuclear accumulation. VDR regulated the expression of β-catenin, cyclin D1 and LEF-1 and directly activated LEF-1 transcription in vitro. Furthermore, nude mice injected with VDR-overexpressing SW480 cells revealed suppression of tumour growth and decreased expression of β-catenin, cyclin D1 and LEF-1. CONCLUSIONS: This study indicated that VDR protected against CRC disease in humans by inhibiting Wnt/β-catenin signalling to control cancer cell invasion and apoptosis, providing new evidence to explore VDR biomarkers or agonists for CRC patient diagnosis and treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10690-z. BioMed Central 2023-04-12 /pmc/articles/PMC10091620/ /pubmed/37046222 http://dx.doi.org/10.1186/s12885-023-10690-z Text en © The Author(s) 2023 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
Yu, Jie
Sun, Qi
Hui, Yi
Xu, Jinping
Shi, Pancheng
Chen, Yu
Chen, Yunzhao
Vitamin D receptor prevents tumour development by regulating the Wnt/β-catenin signalling pathway in human colorectal cancer
title Vitamin D receptor prevents tumour development by regulating the Wnt/β-catenin signalling pathway in human colorectal cancer
title_full Vitamin D receptor prevents tumour development by regulating the Wnt/β-catenin signalling pathway in human colorectal cancer
title_fullStr Vitamin D receptor prevents tumour development by regulating the Wnt/β-catenin signalling pathway in human colorectal cancer
title_full_unstemmed Vitamin D receptor prevents tumour development by regulating the Wnt/β-catenin signalling pathway in human colorectal cancer
title_short Vitamin D receptor prevents tumour development by regulating the Wnt/β-catenin signalling pathway in human colorectal cancer
title_sort vitamin d receptor prevents tumour development by regulating the wnt/β-catenin signalling pathway in human colorectal cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091620/
https://www.ncbi.nlm.nih.gov/pubmed/37046222
http://dx.doi.org/10.1186/s12885-023-10690-z
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