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Ruyiping formula inhibits metastasis via the microRNA-134-SLUG axis in breast cancer

BACKGROUND: Metastasis is the leading cause of death among breast cancer patients. MicroRNA-134 has been reported to have a tumor-suppressive role in breast cancer. Ruyiping (RYP), a traditional Chinese formula, has been shown with the ability to reduce breast cancer metastasis in pre-clinical studi...

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Autores principales: Jiang, Ziwei, Pei, Lixia, Xie, Ying, Ye, Qun, Liang, Xiaoqiang, Ye, Yiyi, Liu, Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258945/
https://www.ncbi.nlm.nih.gov/pubmed/34225726
http://dx.doi.org/10.1186/s12906-021-03365-4
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author Jiang, Ziwei
Pei, Lixia
Xie, Ying
Ye, Qun
Liang, Xiaoqiang
Ye, Yiyi
Liu, Sheng
author_facet Jiang, Ziwei
Pei, Lixia
Xie, Ying
Ye, Qun
Liang, Xiaoqiang
Ye, Yiyi
Liu, Sheng
author_sort Jiang, Ziwei
collection PubMed
description BACKGROUND: Metastasis is the leading cause of death among breast cancer patients. MicroRNA-134 has been reported to have a tumor-suppressive role in breast cancer. Ruyiping (RYP), a traditional Chinese formula, has been shown with the ability to reduce breast cancer metastasis in pre-clinical studies. This present study was designed to examine whether miR-134 was involved in RYP-inhibited breast cancer metastasis. METHODS: The expression of SLUG, E-Cadherin, N-Cadherin and miR-134 in MDA-MB-231 and 4 T1 cells treated with RYP or vehicle control were determined by quantitative realtime-PCR and western blot. Invasiveness determined by transwell assay as well as SLUG gene expression determined by qPCR were detected in cells transfected with chemically synthesized miR-134 mimics or inhibitors. BALB/c mice were injected with 4 T1 cells orthotopically and fed with RYP through gavage. Breast tumor growth, metastasis and tumor expression of EMT markers were detected. RESULTS: Compared with the control, Ruyiping formula significantly inhibited SLUG-regulated breast cancer cells invasion. MiR-134 was induced by RYP in vitro and in vivo and was able to suppress SLUG by targeting its 3’UTR. RYP suppressed SLUG expression and cell invasion through miR-134. In 4 T1 tumor-bearing mice, RYP significantly inhibited 4 T1 tumor growth and lung metastasis, increased the levels of miR-134 and epithelial marker while decreased the levels of SLUG and mesenchymal marker. CONCLUSION: Our data uncovered that Ruyiping formula exerts an anti-metastatic activity against breast cancer cells by regulating SLUG through miR-134. MiR-134-SLUG axis might be a promising strategy in breast cancer therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-021-03365-4.
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spelling pubmed-82589452021-07-06 Ruyiping formula inhibits metastasis via the microRNA-134-SLUG axis in breast cancer Jiang, Ziwei Pei, Lixia Xie, Ying Ye, Qun Liang, Xiaoqiang Ye, Yiyi Liu, Sheng BMC Complement Med Ther Research Article BACKGROUND: Metastasis is the leading cause of death among breast cancer patients. MicroRNA-134 has been reported to have a tumor-suppressive role in breast cancer. Ruyiping (RYP), a traditional Chinese formula, has been shown with the ability to reduce breast cancer metastasis in pre-clinical studies. This present study was designed to examine whether miR-134 was involved in RYP-inhibited breast cancer metastasis. METHODS: The expression of SLUG, E-Cadherin, N-Cadherin and miR-134 in MDA-MB-231 and 4 T1 cells treated with RYP or vehicle control were determined by quantitative realtime-PCR and western blot. Invasiveness determined by transwell assay as well as SLUG gene expression determined by qPCR were detected in cells transfected with chemically synthesized miR-134 mimics or inhibitors. BALB/c mice were injected with 4 T1 cells orthotopically and fed with RYP through gavage. Breast tumor growth, metastasis and tumor expression of EMT markers were detected. RESULTS: Compared with the control, Ruyiping formula significantly inhibited SLUG-regulated breast cancer cells invasion. MiR-134 was induced by RYP in vitro and in vivo and was able to suppress SLUG by targeting its 3’UTR. RYP suppressed SLUG expression and cell invasion through miR-134. In 4 T1 tumor-bearing mice, RYP significantly inhibited 4 T1 tumor growth and lung metastasis, increased the levels of miR-134 and epithelial marker while decreased the levels of SLUG and mesenchymal marker. CONCLUSION: Our data uncovered that Ruyiping formula exerts an anti-metastatic activity against breast cancer cells by regulating SLUG through miR-134. MiR-134-SLUG axis might be a promising strategy in breast cancer therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-021-03365-4. BioMed Central 2021-07-05 /pmc/articles/PMC8258945/ /pubmed/34225726 http://dx.doi.org/10.1186/s12906-021-03365-4 Text en © The Author(s) 2021 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 Article
Jiang, Ziwei
Pei, Lixia
Xie, Ying
Ye, Qun
Liang, Xiaoqiang
Ye, Yiyi
Liu, Sheng
Ruyiping formula inhibits metastasis via the microRNA-134-SLUG axis in breast cancer
title Ruyiping formula inhibits metastasis via the microRNA-134-SLUG axis in breast cancer
title_full Ruyiping formula inhibits metastasis via the microRNA-134-SLUG axis in breast cancer
title_fullStr Ruyiping formula inhibits metastasis via the microRNA-134-SLUG axis in breast cancer
title_full_unstemmed Ruyiping formula inhibits metastasis via the microRNA-134-SLUG axis in breast cancer
title_short Ruyiping formula inhibits metastasis via the microRNA-134-SLUG axis in breast cancer
title_sort ruyiping formula inhibits metastasis via the microrna-134-slug axis in breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258945/
https://www.ncbi.nlm.nih.gov/pubmed/34225726
http://dx.doi.org/10.1186/s12906-021-03365-4
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