miR-370-3p Alleviates Ulcerative Colitis-Related Colorectal Cancer in Mice Through Inhibiting the Inflammatory Response and Epithelial-Mesenchymal Transition

INTRODUCTION: Ulcerative colitis (UC) is a chronic and inflammatory bowel disease. UC-associated colorectal cancer (UC-CRC) is one of the most severe complications of long-standing UC. In the present study, we explored the effects of miR-370-3p on UC-CRC in vivo and investigated its underlying mecha...

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Autores principales: Lin, Lianjie, Wang, Dongxu, Qu, Suxuan, Zhao, Hong, Lin, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078899/
https://www.ncbi.nlm.nih.gov/pubmed/32214798
http://dx.doi.org/10.2147/DDDT.S238124
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author Lin, Lianjie
Wang, Dongxu
Qu, Suxuan
Zhao, Hong
Lin, Yan
author_facet Lin, Lianjie
Wang, Dongxu
Qu, Suxuan
Zhao, Hong
Lin, Yan
author_sort Lin, Lianjie
collection PubMed
description INTRODUCTION: Ulcerative colitis (UC) is a chronic and inflammatory bowel disease. UC-associated colorectal cancer (UC-CRC) is one of the most severe complications of long-standing UC. In the present study, we explored the effects of miR-370-3p on UC-CRC in vivo and investigated its underlying mechanisms in vivo and in vitro. METHODS: Azoxymethane (AOM) and dextran sodium sulfate (DSS) were used to induce UC-CRC in C57BL/6 mice. AOM/DSS-induced mice were treated with 5×10(8) pfu miR-370-3p overexpressing-adenovirus via tail-vein injection every two weeks. RESULTS: We found that miR-370-3p significantly improved the body weights and survival rates and inhibited the tumorigenesis of UC-CRC in AOM/DSS mice. Mechanically, miR-370-3p inhibited AOM/DSS-induced inflammatory response by decreasing tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) through targeting toll-like receptor 4 (TLR4), as demonstrated by down-regulation of TLR4, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and phosphorylated epidermal growth factor receptor (pEGFR). miR-370-3p decreased the expression of tumor-associated proteins, including p53, β-catenin, and ki67 in AOM/DSS-treated mice. Additionally, miR-370-3p remarkably inhibited epithelial-mesenchymal transition (EMT) via increasing E-cadherin expression and reducing N-cadherin and Vimentin expression in vivo. Further studies showed that miR-370-3p repressed proliferation and EMT of colon cancer cells in vitro. Moreover, we proved that miR-370-3p decreased the expression of tumor-associated proteins and reversed EMT by regulating β-catenin in colon cancer cells. CONCLUSION: Taken together, miR-370-3p alleviated UC-CRC by inhibiting the inflammatory response and EMT in mice, which suggested miR-370-3p as a novel potential target for UC-CRC therapy.
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spelling pubmed-70788992020-03-25 miR-370-3p Alleviates Ulcerative Colitis-Related Colorectal Cancer in Mice Through Inhibiting the Inflammatory Response and Epithelial-Mesenchymal Transition Lin, Lianjie Wang, Dongxu Qu, Suxuan Zhao, Hong Lin, Yan Drug Des Devel Ther Original Research INTRODUCTION: Ulcerative colitis (UC) is a chronic and inflammatory bowel disease. UC-associated colorectal cancer (UC-CRC) is one of the most severe complications of long-standing UC. In the present study, we explored the effects of miR-370-3p on UC-CRC in vivo and investigated its underlying mechanisms in vivo and in vitro. METHODS: Azoxymethane (AOM) and dextran sodium sulfate (DSS) were used to induce UC-CRC in C57BL/6 mice. AOM/DSS-induced mice were treated with 5×10(8) pfu miR-370-3p overexpressing-adenovirus via tail-vein injection every two weeks. RESULTS: We found that miR-370-3p significantly improved the body weights and survival rates and inhibited the tumorigenesis of UC-CRC in AOM/DSS mice. Mechanically, miR-370-3p inhibited AOM/DSS-induced inflammatory response by decreasing tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) through targeting toll-like receptor 4 (TLR4), as demonstrated by down-regulation of TLR4, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and phosphorylated epidermal growth factor receptor (pEGFR). miR-370-3p decreased the expression of tumor-associated proteins, including p53, β-catenin, and ki67 in AOM/DSS-treated mice. Additionally, miR-370-3p remarkably inhibited epithelial-mesenchymal transition (EMT) via increasing E-cadherin expression and reducing N-cadherin and Vimentin expression in vivo. Further studies showed that miR-370-3p repressed proliferation and EMT of colon cancer cells in vitro. Moreover, we proved that miR-370-3p decreased the expression of tumor-associated proteins and reversed EMT by regulating β-catenin in colon cancer cells. CONCLUSION: Taken together, miR-370-3p alleviated UC-CRC by inhibiting the inflammatory response and EMT in mice, which suggested miR-370-3p as a novel potential target for UC-CRC therapy. Dove 2020-03-13 /pmc/articles/PMC7078899/ /pubmed/32214798 http://dx.doi.org/10.2147/DDDT.S238124 Text en © 2020 Lin et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Lin, Lianjie
Wang, Dongxu
Qu, Suxuan
Zhao, Hong
Lin, Yan
miR-370-3p Alleviates Ulcerative Colitis-Related Colorectal Cancer in Mice Through Inhibiting the Inflammatory Response and Epithelial-Mesenchymal Transition
title miR-370-3p Alleviates Ulcerative Colitis-Related Colorectal Cancer in Mice Through Inhibiting the Inflammatory Response and Epithelial-Mesenchymal Transition
title_full miR-370-3p Alleviates Ulcerative Colitis-Related Colorectal Cancer in Mice Through Inhibiting the Inflammatory Response and Epithelial-Mesenchymal Transition
title_fullStr miR-370-3p Alleviates Ulcerative Colitis-Related Colorectal Cancer in Mice Through Inhibiting the Inflammatory Response and Epithelial-Mesenchymal Transition
title_full_unstemmed miR-370-3p Alleviates Ulcerative Colitis-Related Colorectal Cancer in Mice Through Inhibiting the Inflammatory Response and Epithelial-Mesenchymal Transition
title_short miR-370-3p Alleviates Ulcerative Colitis-Related Colorectal Cancer in Mice Through Inhibiting the Inflammatory Response and Epithelial-Mesenchymal Transition
title_sort mir-370-3p alleviates ulcerative colitis-related colorectal cancer in mice through inhibiting the inflammatory response and epithelial-mesenchymal transition
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078899/
https://www.ncbi.nlm.nih.gov/pubmed/32214798
http://dx.doi.org/10.2147/DDDT.S238124
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