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miR-615-3p promotes the epithelial-mesenchymal transition and metastasis of breast cancer by targeting PICK1/TGFBRI axis

BACKGROUND: Increasing evidence indicates that epithelial-mesenchymal transition (EMT) can be regulated by microRNAs (miRNAs). miR-615-3p was shown to be involved in tumor development. However, the role of miR-615-3p in the metastasis of breast cancer remains largely unknown. METHODS: The expression...

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Autores principales: Lei, Bo, Wang, Dandan, Zhang, Ming, Deng, Yuwei, Jiang, Huijie, Li, Yiwen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183699/
https://www.ncbi.nlm.nih.gov/pubmed/32336285
http://dx.doi.org/10.1186/s13046-020-01571-5
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author Lei, Bo
Wang, Dandan
Zhang, Ming
Deng, Yuwei
Jiang, Huijie
Li, Yiwen
author_facet Lei, Bo
Wang, Dandan
Zhang, Ming
Deng, Yuwei
Jiang, Huijie
Li, Yiwen
author_sort Lei, Bo
collection PubMed
description BACKGROUND: Increasing evidence indicates that epithelial-mesenchymal transition (EMT) can be regulated by microRNAs (miRNAs). miR-615-3p was shown to be involved in tumor development. However, the role of miR-615-3p in the metastasis of breast cancer remains largely unknown. METHODS: The expression of miR-615-3p in breast cancer cells and tissues was assessed by qRT-PCR and situ hybridization assays. Effects of miR-615-3p on tumor metastasis were evaluated with experiments in vitro and mouse model. EMT markers were detected by western blot and immunofluorescence assays. Molecular mechanism of miR-615-3p in the regulation of breast cancer cell metastasis was analyzed by Western Blot, Co-immunoprecipitation, and Luciferase assay. RESULTS: In the present study, we found that miR-615-3p was significantly elevated in breast cancer cells and tissues, especially in those with metastasis. In breast cancer cell lines, stable overexpression of miR-615-3p was sufficient to promote cell motility in vitro, and pulmonary metastasis in vivo, accompanied by the reduced expression of epithelial markers and the increased levels of mesenchymal markers. Further studies revealed that the reintroduction of miR-615-3p increased the downstream signaling of TGF-β, the type I receptor (TGFBRI) by targeting the 3′-untranslated regions (3′-UTR) of PICK1. PICK1 inhibits the binding of DICER1 to Smad2/3 and the processing of pre-miR-615-3p to mature miR-615-3p in breast cancer cells, thus exerting a negative feedback loop. CONCLUSIONS: Our data highlight an important role of miR-615-3p in the molecular etiology of breast cancer, and implicate the potential application of miR-615-3p in cancer therapy.
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spelling pubmed-71836992020-04-29 miR-615-3p promotes the epithelial-mesenchymal transition and metastasis of breast cancer by targeting PICK1/TGFBRI axis Lei, Bo Wang, Dandan Zhang, Ming Deng, Yuwei Jiang, Huijie Li, Yiwen J Exp Clin Cancer Res Research BACKGROUND: Increasing evidence indicates that epithelial-mesenchymal transition (EMT) can be regulated by microRNAs (miRNAs). miR-615-3p was shown to be involved in tumor development. However, the role of miR-615-3p in the metastasis of breast cancer remains largely unknown. METHODS: The expression of miR-615-3p in breast cancer cells and tissues was assessed by qRT-PCR and situ hybridization assays. Effects of miR-615-3p on tumor metastasis were evaluated with experiments in vitro and mouse model. EMT markers were detected by western blot and immunofluorescence assays. Molecular mechanism of miR-615-3p in the regulation of breast cancer cell metastasis was analyzed by Western Blot, Co-immunoprecipitation, and Luciferase assay. RESULTS: In the present study, we found that miR-615-3p was significantly elevated in breast cancer cells and tissues, especially in those with metastasis. In breast cancer cell lines, stable overexpression of miR-615-3p was sufficient to promote cell motility in vitro, and pulmonary metastasis in vivo, accompanied by the reduced expression of epithelial markers and the increased levels of mesenchymal markers. Further studies revealed that the reintroduction of miR-615-3p increased the downstream signaling of TGF-β, the type I receptor (TGFBRI) by targeting the 3′-untranslated regions (3′-UTR) of PICK1. PICK1 inhibits the binding of DICER1 to Smad2/3 and the processing of pre-miR-615-3p to mature miR-615-3p in breast cancer cells, thus exerting a negative feedback loop. CONCLUSIONS: Our data highlight an important role of miR-615-3p in the molecular etiology of breast cancer, and implicate the potential application of miR-615-3p in cancer therapy. BioMed Central 2020-04-26 /pmc/articles/PMC7183699/ /pubmed/32336285 http://dx.doi.org/10.1186/s13046-020-01571-5 Text en © The Author(s) 2020 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/. The Creative Commons Public Domain Dedication waiver (http://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
Lei, Bo
Wang, Dandan
Zhang, Ming
Deng, Yuwei
Jiang, Huijie
Li, Yiwen
miR-615-3p promotes the epithelial-mesenchymal transition and metastasis of breast cancer by targeting PICK1/TGFBRI axis
title miR-615-3p promotes the epithelial-mesenchymal transition and metastasis of breast cancer by targeting PICK1/TGFBRI axis
title_full miR-615-3p promotes the epithelial-mesenchymal transition and metastasis of breast cancer by targeting PICK1/TGFBRI axis
title_fullStr miR-615-3p promotes the epithelial-mesenchymal transition and metastasis of breast cancer by targeting PICK1/TGFBRI axis
title_full_unstemmed miR-615-3p promotes the epithelial-mesenchymal transition and metastasis of breast cancer by targeting PICK1/TGFBRI axis
title_short miR-615-3p promotes the epithelial-mesenchymal transition and metastasis of breast cancer by targeting PICK1/TGFBRI axis
title_sort mir-615-3p promotes the epithelial-mesenchymal transition and metastasis of breast cancer by targeting pick1/tgfbri axis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183699/
https://www.ncbi.nlm.nih.gov/pubmed/32336285
http://dx.doi.org/10.1186/s13046-020-01571-5
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