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MicroRNA‐338‐5p reverses chemoresistance and inhibits invasion of esophageal squamous cell carcinoma cells by targeting Id‐1
5‐Fluorouracil (5‐FU) is a chemotherapeutic agent commonly used to treat esophageal squamous cell carcinoma (ESCC), but acquisition of chemoresistance frequently occurs and the underlying mechanisms are not fully understood. We found that microRNA (miR)‐338‐5p was underexpressed in ESCC cells with a...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890449/ https://www.ncbi.nlm.nih.gov/pubmed/31646712 http://dx.doi.org/10.1111/cas.14220 |
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author | Han, Liang Cui, Di Li, Bin Xu, Wen Wen Lam, Alfred King Y. Chan, Kin Tak Zhu, Yun Lee, Nikki P.Y. Law, Simon Y.K. Guan, Xin Yuan Qin, Yan Ru Chan, Kwok Wah Ma, Stephanie Tsao, Sai Wah Cheung, Annie L.M. |
author_facet | Han, Liang Cui, Di Li, Bin Xu, Wen Wen Lam, Alfred King Y. Chan, Kin Tak Zhu, Yun Lee, Nikki P.Y. Law, Simon Y.K. Guan, Xin Yuan Qin, Yan Ru Chan, Kwok Wah Ma, Stephanie Tsao, Sai Wah Cheung, Annie L.M. |
author_sort | Han, Liang |
collection | PubMed |
description | 5‐Fluorouracil (5‐FU) is a chemotherapeutic agent commonly used to treat esophageal squamous cell carcinoma (ESCC), but acquisition of chemoresistance frequently occurs and the underlying mechanisms are not fully understood. We found that microRNA (miR)‐338‐5p was underexpressed in ESCC cells with acquired 5‐FU chemoresistance. Forced expression of miR‐338‐5p in these cells resulted in downregulation of Id‐1, and restoration of both in vitro and in vivo sensitivity to 5‐FU treatment. The effects were abolished by reexpression of Id‐1. In contrast, miR‐338‐5p knockdown induced 5‐FU resistance in chemosensitive esophageal cell lines, and knockdown of both miR‐338‐5p and Id‐1 resensitized the cells to 5‐FU. In addition, miR‐338‐5p had suppressive effects on migration and invasion of ESCC cells. Luciferase reporter assay confirmed a direct interaction between miR‐338‐5p and the 3′‐UTR of Id‐1. We also found that miR‐338‐5p was significantly downregulated in tumor tissue and serum samples of patients with ESCC. Notably, low serum miR‐338‐5p expression level was associated with poorer survival and poor response to 5‐FU/cisplatin‐based neoadjuvant chemoradiotherapy. In summary, we found that miR‐338‐5p can modulate 5‐FU chemoresistance and inhibit invasion‐related functions in ESCC by negatively regulating Id‐1, and that serum miR‐338‐5p could be a novel noninvasive prognostic and predictive biomarker in ESCC. |
format | Online Article Text |
id | pubmed-6890449 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68904492019-12-12 MicroRNA‐338‐5p reverses chemoresistance and inhibits invasion of esophageal squamous cell carcinoma cells by targeting Id‐1 Han, Liang Cui, Di Li, Bin Xu, Wen Wen Lam, Alfred King Y. Chan, Kin Tak Zhu, Yun Lee, Nikki P.Y. Law, Simon Y.K. Guan, Xin Yuan Qin, Yan Ru Chan, Kwok Wah Ma, Stephanie Tsao, Sai Wah Cheung, Annie L.M. Cancer Sci Original Articles 5‐Fluorouracil (5‐FU) is a chemotherapeutic agent commonly used to treat esophageal squamous cell carcinoma (ESCC), but acquisition of chemoresistance frequently occurs and the underlying mechanisms are not fully understood. We found that microRNA (miR)‐338‐5p was underexpressed in ESCC cells with acquired 5‐FU chemoresistance. Forced expression of miR‐338‐5p in these cells resulted in downregulation of Id‐1, and restoration of both in vitro and in vivo sensitivity to 5‐FU treatment. The effects were abolished by reexpression of Id‐1. In contrast, miR‐338‐5p knockdown induced 5‐FU resistance in chemosensitive esophageal cell lines, and knockdown of both miR‐338‐5p and Id‐1 resensitized the cells to 5‐FU. In addition, miR‐338‐5p had suppressive effects on migration and invasion of ESCC cells. Luciferase reporter assay confirmed a direct interaction between miR‐338‐5p and the 3′‐UTR of Id‐1. We also found that miR‐338‐5p was significantly downregulated in tumor tissue and serum samples of patients with ESCC. Notably, low serum miR‐338‐5p expression level was associated with poorer survival and poor response to 5‐FU/cisplatin‐based neoadjuvant chemoradiotherapy. In summary, we found that miR‐338‐5p can modulate 5‐FU chemoresistance and inhibit invasion‐related functions in ESCC by negatively regulating Id‐1, and that serum miR‐338‐5p could be a novel noninvasive prognostic and predictive biomarker in ESCC. John Wiley and Sons Inc. 2019-11-17 2019-12 /pmc/articles/PMC6890449/ /pubmed/31646712 http://dx.doi.org/10.1111/cas.14220 Text en © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Han, Liang Cui, Di Li, Bin Xu, Wen Wen Lam, Alfred King Y. Chan, Kin Tak Zhu, Yun Lee, Nikki P.Y. Law, Simon Y.K. Guan, Xin Yuan Qin, Yan Ru Chan, Kwok Wah Ma, Stephanie Tsao, Sai Wah Cheung, Annie L.M. MicroRNA‐338‐5p reverses chemoresistance and inhibits invasion of esophageal squamous cell carcinoma cells by targeting Id‐1 |
title | MicroRNA‐338‐5p reverses chemoresistance and inhibits invasion of esophageal squamous cell carcinoma cells by targeting Id‐1 |
title_full | MicroRNA‐338‐5p reverses chemoresistance and inhibits invasion of esophageal squamous cell carcinoma cells by targeting Id‐1 |
title_fullStr | MicroRNA‐338‐5p reverses chemoresistance and inhibits invasion of esophageal squamous cell carcinoma cells by targeting Id‐1 |
title_full_unstemmed | MicroRNA‐338‐5p reverses chemoresistance and inhibits invasion of esophageal squamous cell carcinoma cells by targeting Id‐1 |
title_short | MicroRNA‐338‐5p reverses chemoresistance and inhibits invasion of esophageal squamous cell carcinoma cells by targeting Id‐1 |
title_sort | microrna‐338‐5p reverses chemoresistance and inhibits invasion of esophageal squamous cell carcinoma cells by targeting id‐1 |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890449/ https://www.ncbi.nlm.nih.gov/pubmed/31646712 http://dx.doi.org/10.1111/cas.14220 |
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