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Amentoflavone inhibits colorectal cancer epithelial-mesenchymal transition via the miR-16-5p/HMGA2/β-catenin pathway
BACKGROUND: Amentoflavone is a type of bioflavonoid that exists in many Chinese medicines and has anti-inflammatory, antioxidant, antiviral, and anticancer effects. However, the effect of amentoflavone on epithelial to mesenchymal transition (EMT) in human colorectal cancer (CRC) has not been studie...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9577732/ https://www.ncbi.nlm.nih.gov/pubmed/36267717 http://dx.doi.org/10.21037/atm-22-3035 |
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author | Cai, Kai Yang, Yang Guo, Zi-Jian Cai, Rui-Lin Hashida, Hiroki Li, Hong-Xia |
author_facet | Cai, Kai Yang, Yang Guo, Zi-Jian Cai, Rui-Lin Hashida, Hiroki Li, Hong-Xia |
author_sort | Cai, Kai |
collection | PubMed |
description | BACKGROUND: Amentoflavone is a type of bioflavonoid that exists in many Chinese medicines and has anti-inflammatory, antioxidant, antiviral, and anticancer effects. However, the effect of amentoflavone on epithelial to mesenchymal transition (EMT) in human colorectal cancer (CRC) has not been studied. In this study, we aim to explore the effect of amentoflavone on EMT in CRC. METHODS: The effects of long noncoding RNA (lncRNA) miR-16-5p on proliferation, migration, and invasion were determined by in vitro and in vivo experiments. A luciferase reporter assay was carried out to reveal the interaction between miR-16-5p and targeted genes. Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate the expression of miR-16-5p. A western blot assay was used to detect the expression of targeted genes in CRC cells. RESULTS: The results showed that amentoflavone significantly inhibited CRC migration, invasion, and EMT by increasing miR-16-5p expression. Mechanistically, amentoflavone induced inactivation of the Wnt/β-catenin pathway via miR-16-5p, directly targeting 3'-UTR of HMGA2 to suppress HMGA2 expression in CRC. Clinically, combined miR-16-5p and HMGA2 levels may serve as a predictor for poor prognosis in patients with CRC. Furthermore, an in vivo PDX model suggested that amentoflavone exhibited antitumor effects in vivo via the miR-16-5p/HMGA2/β-catenin pathway. CONCLUSIONS: This is the first study to show that amentoflavone inhibits CRC EMT via the miR-16/HMGA2/β-catenin pathway. Amentoflavone may be beneficial in treating CRC patients in the clinic. |
format | Online Article Text |
id | pubmed-9577732 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-95777322022-10-19 Amentoflavone inhibits colorectal cancer epithelial-mesenchymal transition via the miR-16-5p/HMGA2/β-catenin pathway Cai, Kai Yang, Yang Guo, Zi-Jian Cai, Rui-Lin Hashida, Hiroki Li, Hong-Xia Ann Transl Med Original Article BACKGROUND: Amentoflavone is a type of bioflavonoid that exists in many Chinese medicines and has anti-inflammatory, antioxidant, antiviral, and anticancer effects. However, the effect of amentoflavone on epithelial to mesenchymal transition (EMT) in human colorectal cancer (CRC) has not been studied. In this study, we aim to explore the effect of amentoflavone on EMT in CRC. METHODS: The effects of long noncoding RNA (lncRNA) miR-16-5p on proliferation, migration, and invasion were determined by in vitro and in vivo experiments. A luciferase reporter assay was carried out to reveal the interaction between miR-16-5p and targeted genes. Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate the expression of miR-16-5p. A western blot assay was used to detect the expression of targeted genes in CRC cells. RESULTS: The results showed that amentoflavone significantly inhibited CRC migration, invasion, and EMT by increasing miR-16-5p expression. Mechanistically, amentoflavone induced inactivation of the Wnt/β-catenin pathway via miR-16-5p, directly targeting 3'-UTR of HMGA2 to suppress HMGA2 expression in CRC. Clinically, combined miR-16-5p and HMGA2 levels may serve as a predictor for poor prognosis in patients with CRC. Furthermore, an in vivo PDX model suggested that amentoflavone exhibited antitumor effects in vivo via the miR-16-5p/HMGA2/β-catenin pathway. CONCLUSIONS: This is the first study to show that amentoflavone inhibits CRC EMT via the miR-16/HMGA2/β-catenin pathway. Amentoflavone may be beneficial in treating CRC patients in the clinic. AME Publishing Company 2022-09 /pmc/articles/PMC9577732/ /pubmed/36267717 http://dx.doi.org/10.21037/atm-22-3035 Text en 2022 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Cai, Kai Yang, Yang Guo, Zi-Jian Cai, Rui-Lin Hashida, Hiroki Li, Hong-Xia Amentoflavone inhibits colorectal cancer epithelial-mesenchymal transition via the miR-16-5p/HMGA2/β-catenin pathway |
title | Amentoflavone inhibits colorectal cancer epithelial-mesenchymal transition via the miR-16-5p/HMGA2/β-catenin pathway |
title_full | Amentoflavone inhibits colorectal cancer epithelial-mesenchymal transition via the miR-16-5p/HMGA2/β-catenin pathway |
title_fullStr | Amentoflavone inhibits colorectal cancer epithelial-mesenchymal transition via the miR-16-5p/HMGA2/β-catenin pathway |
title_full_unstemmed | Amentoflavone inhibits colorectal cancer epithelial-mesenchymal transition via the miR-16-5p/HMGA2/β-catenin pathway |
title_short | Amentoflavone inhibits colorectal cancer epithelial-mesenchymal transition via the miR-16-5p/HMGA2/β-catenin pathway |
title_sort | amentoflavone inhibits colorectal cancer epithelial-mesenchymal transition via the mir-16-5p/hmga2/β-catenin pathway |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9577732/ https://www.ncbi.nlm.nih.gov/pubmed/36267717 http://dx.doi.org/10.21037/atm-22-3035 |
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