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The Regulation and Function of miR-21-FOXO3a-miR-34b/c Signaling in Breast Cancer
Upregulation of miR-21 (microRNA-21) and downregulation of miR-34b/c have been found in breast cancer (BC). However, their regulation mechanism and function roles in BC have not been fully addressed. Here, we report that miR-21 levels were inversely correlated with miR-34b/c levels in BC. MiR-21 upr...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346885/ https://www.ncbi.nlm.nih.gov/pubmed/25647415 http://dx.doi.org/10.3390/ijms16023148 |
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author | Liu, Xiangyan Feng, Jie Tang, Lili Liao, Liqiu Xu, Qing Zhu, Shaihong |
author_facet | Liu, Xiangyan Feng, Jie Tang, Lili Liao, Liqiu Xu, Qing Zhu, Shaihong |
author_sort | Liu, Xiangyan |
collection | PubMed |
description | Upregulation of miR-21 (microRNA-21) and downregulation of miR-34b/c have been found in breast cancer (BC). However, their regulation mechanism and function roles in BC have not been fully addressed. Here, we report that miR-21 levels were inversely correlated with miR-34b/c levels in BC. MiR-21 upregulation contributes to PTEN downregulation, which is beneficial for the activation of PI3K/AKT signaling. The activation of AKT phosphorylates FOXO3a, triggering relocalization of FOXO3a proteins from the nucleus to the cytoplasm. FOXO3a is a newly identified transcription factor responsible for miR-34b/c expression. Downregulation of nuclear FOXO3a decreased the expression levels of miR-34b and miR-34c in breast cancer cells, in which p53 was mutated. We also found upregulation of circulating miR-21 and downregulation of circulating miR-34b/c in BC patients’ serum. More importantly, we showed that systemic delivery of miR-34b/c or with anti-miR-21 significantly inhibited breast tumor growth in vivo. These results suggest that high circulating levels of miR-21 and low levels of miR-34b/c may provide potential biomarkers for BC diagnosis, and systemic delivery of miR-34b/c has potential as a therapeutic option for BC treatment. |
format | Online Article Text |
id | pubmed-4346885 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-43468852015-04-03 The Regulation and Function of miR-21-FOXO3a-miR-34b/c Signaling in Breast Cancer Liu, Xiangyan Feng, Jie Tang, Lili Liao, Liqiu Xu, Qing Zhu, Shaihong Int J Mol Sci Article Upregulation of miR-21 (microRNA-21) and downregulation of miR-34b/c have been found in breast cancer (BC). However, their regulation mechanism and function roles in BC have not been fully addressed. Here, we report that miR-21 levels were inversely correlated with miR-34b/c levels in BC. MiR-21 upregulation contributes to PTEN downregulation, which is beneficial for the activation of PI3K/AKT signaling. The activation of AKT phosphorylates FOXO3a, triggering relocalization of FOXO3a proteins from the nucleus to the cytoplasm. FOXO3a is a newly identified transcription factor responsible for miR-34b/c expression. Downregulation of nuclear FOXO3a decreased the expression levels of miR-34b and miR-34c in breast cancer cells, in which p53 was mutated. We also found upregulation of circulating miR-21 and downregulation of circulating miR-34b/c in BC patients’ serum. More importantly, we showed that systemic delivery of miR-34b/c or with anti-miR-21 significantly inhibited breast tumor growth in vivo. These results suggest that high circulating levels of miR-21 and low levels of miR-34b/c may provide potential biomarkers for BC diagnosis, and systemic delivery of miR-34b/c has potential as a therapeutic option for BC treatment. MDPI 2015-01-30 /pmc/articles/PMC4346885/ /pubmed/25647415 http://dx.doi.org/10.3390/ijms16023148 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Xiangyan Feng, Jie Tang, Lili Liao, Liqiu Xu, Qing Zhu, Shaihong The Regulation and Function of miR-21-FOXO3a-miR-34b/c Signaling in Breast Cancer |
title | The Regulation and Function of miR-21-FOXO3a-miR-34b/c Signaling in Breast Cancer |
title_full | The Regulation and Function of miR-21-FOXO3a-miR-34b/c Signaling in Breast Cancer |
title_fullStr | The Regulation and Function of miR-21-FOXO3a-miR-34b/c Signaling in Breast Cancer |
title_full_unstemmed | The Regulation and Function of miR-21-FOXO3a-miR-34b/c Signaling in Breast Cancer |
title_short | The Regulation and Function of miR-21-FOXO3a-miR-34b/c Signaling in Breast Cancer |
title_sort | regulation and function of mir-21-foxo3a-mir-34b/c signaling in breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346885/ https://www.ncbi.nlm.nih.gov/pubmed/25647415 http://dx.doi.org/10.3390/ijms16023148 |
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