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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...

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Autores principales: Liu, Xiangyan, Feng, Jie, Tang, Lili, Liao, Liqiu, Xu, Qing, Zhu, Shaihong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
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.
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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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