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L-Fucose inhibits the progression of cholangiocarcinoma by causing microRNA-200b overexpression

BACKGROUND: Cholangiocarcinoma (CCA) is a malignant biliary tract tumor with an extremely poor prognosis. There is an urgent demand to explore novel therapeutic strategies. L-fucose has been confirmed to participate in anti-inflammation and antitumor activities. However, the effect of L-fucose on th...

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Autores principales: Zhu, Biqiang, Zheng, Jingjing, Hong, Gaichao, Bai, Tao, Qian, Wei, Liu, Jinsong, Hou, Xiaohua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10106127/
https://www.ncbi.nlm.nih.gov/pubmed/36728287
http://dx.doi.org/10.1097/CM9.0000000000002368
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author Zhu, Biqiang
Zheng, Jingjing
Hong, Gaichao
Bai, Tao
Qian, Wei
Liu, Jinsong
Hou, Xiaohua
author_facet Zhu, Biqiang
Zheng, Jingjing
Hong, Gaichao
Bai, Tao
Qian, Wei
Liu, Jinsong
Hou, Xiaohua
author_sort Zhu, Biqiang
collection PubMed
description BACKGROUND: Cholangiocarcinoma (CCA) is a malignant biliary tract tumor with an extremely poor prognosis. There is an urgent demand to explore novel therapeutic strategies. L-fucose has been confirmed to participate in anti-inflammation and antitumor activities. However, the effect of L-fucose on the progression of CCA has not been well investigated. This study aimed to determine whether L-fucose induced the inhibition of CCA and its possible mechanism. METHODS: The anti-growth activity was determined using Cell Counting Kit-8 assay, colony formation assays, Annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assay, and cell cycle analysis. The anti-metastasis activity was determined by wound healing, transwell, and invasion assays. The anti-angiogenesis activity was determined by tube formation and transwell assays. MicroRNAs that may be involved in the L-fucose-induced CCA inhibition was analyzed using bioinformatics methods. The preclinical therapeutic efficacy was mainly estimated by ultrasound in xenograft nude mouse models. Differences were analyzed via Student's t test or one-way analysis of variance. RESULTS: L-Fucose induced apoptosis and G0/G1 cell cycle arrest, inhibited cell epithelial-mesenchymal transition of CCA cells, and additionally inhibited tube formation of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner, leading to a decrease in cell proliferation, metastasis, and angiogenesis. Mechanistically, L-fucose induced microRNA-200b (miR-200b) upregulation, and mitogen-activated protein kinase 7 (MAPK7) downregulation was found to be targeted by miR-200b, with decreased cell proliferation and metastasis. Additionally, phosphorylated signal transducer and activator of transcription 3 was found to be downregulated after L-fucose treatment. Finally, in vivo experiments in CCA xenograft models also confirmed the antitumor properties of L-fucose. CONCLUSION: L-Fucose inhibited the progression of CCA via the miR-200b/MAPK7 and signal transducer and activator of transcription 3 signaling pathways.
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spelling pubmed-101061272023-04-17 L-Fucose inhibits the progression of cholangiocarcinoma by causing microRNA-200b overexpression Zhu, Biqiang Zheng, Jingjing Hong, Gaichao Bai, Tao Qian, Wei Liu, Jinsong Hou, Xiaohua Chin Med J (Engl) Original Articles BACKGROUND: Cholangiocarcinoma (CCA) is a malignant biliary tract tumor with an extremely poor prognosis. There is an urgent demand to explore novel therapeutic strategies. L-fucose has been confirmed to participate in anti-inflammation and antitumor activities. However, the effect of L-fucose on the progression of CCA has not been well investigated. This study aimed to determine whether L-fucose induced the inhibition of CCA and its possible mechanism. METHODS: The anti-growth activity was determined using Cell Counting Kit-8 assay, colony formation assays, Annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assay, and cell cycle analysis. The anti-metastasis activity was determined by wound healing, transwell, and invasion assays. The anti-angiogenesis activity was determined by tube formation and transwell assays. MicroRNAs that may be involved in the L-fucose-induced CCA inhibition was analyzed using bioinformatics methods. The preclinical therapeutic efficacy was mainly estimated by ultrasound in xenograft nude mouse models. Differences were analyzed via Student's t test or one-way analysis of variance. RESULTS: L-Fucose induced apoptosis and G0/G1 cell cycle arrest, inhibited cell epithelial-mesenchymal transition of CCA cells, and additionally inhibited tube formation of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner, leading to a decrease in cell proliferation, metastasis, and angiogenesis. Mechanistically, L-fucose induced microRNA-200b (miR-200b) upregulation, and mitogen-activated protein kinase 7 (MAPK7) downregulation was found to be targeted by miR-200b, with decreased cell proliferation and metastasis. Additionally, phosphorylated signal transducer and activator of transcription 3 was found to be downregulated after L-fucose treatment. Finally, in vivo experiments in CCA xenograft models also confirmed the antitumor properties of L-fucose. CONCLUSION: L-Fucose inhibited the progression of CCA via the miR-200b/MAPK7 and signal transducer and activator of transcription 3 signaling pathways. Lippincott Williams & Wilkins 2022-12-20 2023-01-09 /pmc/articles/PMC10106127/ /pubmed/36728287 http://dx.doi.org/10.1097/CM9.0000000000002368 Text en Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Original Articles
Zhu, Biqiang
Zheng, Jingjing
Hong, Gaichao
Bai, Tao
Qian, Wei
Liu, Jinsong
Hou, Xiaohua
L-Fucose inhibits the progression of cholangiocarcinoma by causing microRNA-200b overexpression
title L-Fucose inhibits the progression of cholangiocarcinoma by causing microRNA-200b overexpression
title_full L-Fucose inhibits the progression of cholangiocarcinoma by causing microRNA-200b overexpression
title_fullStr L-Fucose inhibits the progression of cholangiocarcinoma by causing microRNA-200b overexpression
title_full_unstemmed L-Fucose inhibits the progression of cholangiocarcinoma by causing microRNA-200b overexpression
title_short L-Fucose inhibits the progression of cholangiocarcinoma by causing microRNA-200b overexpression
title_sort l-fucose inhibits the progression of cholangiocarcinoma by causing microrna-200b overexpression
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10106127/
https://www.ncbi.nlm.nih.gov/pubmed/36728287
http://dx.doi.org/10.1097/CM9.0000000000002368
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