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EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer via the Inhibition of FOXO1 and the p53 Signaling Pathway

Breast cancer (BC) is the most common gynecologic tumor worldwide where aberrant expression of microRNAs (miRNAs) is frequently involved. Here, we evaluated the function of miR-375 on BC development and the molecules implicated. Differentially expressed genes between tumor and paired normal tissues...

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Autores principales: Guan, Xin, Shi, Aiping, Zou, Yabin, Sun, Meiyang, Zhan, Yue, Dong, Yi, Fan, Zhimin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041054/
https://www.ncbi.nlm.nih.gov/pubmed/33854524
http://dx.doi.org/10.3389/fgene.2021.633756
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author Guan, Xin
Shi, Aiping
Zou, Yabin
Sun, Meiyang
Zhan, Yue
Dong, Yi
Fan, Zhimin
author_facet Guan, Xin
Shi, Aiping
Zou, Yabin
Sun, Meiyang
Zhan, Yue
Dong, Yi
Fan, Zhimin
author_sort Guan, Xin
collection PubMed
description Breast cancer (BC) is the most common gynecologic tumor worldwide where aberrant expression of microRNAs (miRNAs) is frequently involved. Here, we evaluated the function of miR-375 on BC development and the molecules implicated. Differentially expressed genes between tumor and paired normal tissues from BC patients were screened out by microarray analyses. miR-375 was abundantly expressed in BC tissues and cells, and it was correlated with the poor prognosis of patients. Downregulation of miR-375 was introduced into BC cell lines MCF-7 and HCC1954, after which the viability, colony formation, migration, and invasion were suppressed, while the apoptosis of cells was increased, and the xenograft tumors in nude mice were reduced as well. EZH2 increased methylation and phosphorylation of signal transducer and activator of transcription 3 (STAT3) and increased transcription activity of miR-375, while miR-375 directly targeted FOXO1. Either overexpression of EZH2 or downregulation of FOXO1 blocked the functions of anti-miR-375 in cells and animals. FOXO1 was found as an activator of the p53 signaling pathway. This study showed that miR-375 is an important oncogene in BC. EZH2 is an upstream regulator of miR-375 through mediating the methylation of STAT3, while FOXO1 is a downstream target mRNA of miR-375 that activates the p53 signaling pathway to suppress BC development.
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spelling pubmed-80410542021-04-13 EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer via the Inhibition of FOXO1 and the p53 Signaling Pathway Guan, Xin Shi, Aiping Zou, Yabin Sun, Meiyang Zhan, Yue Dong, Yi Fan, Zhimin Front Genet Genetics Breast cancer (BC) is the most common gynecologic tumor worldwide where aberrant expression of microRNAs (miRNAs) is frequently involved. Here, we evaluated the function of miR-375 on BC development and the molecules implicated. Differentially expressed genes between tumor and paired normal tissues from BC patients were screened out by microarray analyses. miR-375 was abundantly expressed in BC tissues and cells, and it was correlated with the poor prognosis of patients. Downregulation of miR-375 was introduced into BC cell lines MCF-7 and HCC1954, after which the viability, colony formation, migration, and invasion were suppressed, while the apoptosis of cells was increased, and the xenograft tumors in nude mice were reduced as well. EZH2 increased methylation and phosphorylation of signal transducer and activator of transcription 3 (STAT3) and increased transcription activity of miR-375, while miR-375 directly targeted FOXO1. Either overexpression of EZH2 or downregulation of FOXO1 blocked the functions of anti-miR-375 in cells and animals. FOXO1 was found as an activator of the p53 signaling pathway. This study showed that miR-375 is an important oncogene in BC. EZH2 is an upstream regulator of miR-375 through mediating the methylation of STAT3, while FOXO1 is a downstream target mRNA of miR-375 that activates the p53 signaling pathway to suppress BC development. Frontiers Media S.A. 2021-03-29 /pmc/articles/PMC8041054/ /pubmed/33854524 http://dx.doi.org/10.3389/fgene.2021.633756 Text en Copyright © 2021 Guan, Shi, Zou, Sun, Zhan, Dong and Fan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Guan, Xin
Shi, Aiping
Zou, Yabin
Sun, Meiyang
Zhan, Yue
Dong, Yi
Fan, Zhimin
EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer via the Inhibition of FOXO1 and the p53 Signaling Pathway
title EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer via the Inhibition of FOXO1 and the p53 Signaling Pathway
title_full EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer via the Inhibition of FOXO1 and the p53 Signaling Pathway
title_fullStr EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer via the Inhibition of FOXO1 and the p53 Signaling Pathway
title_full_unstemmed EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer via the Inhibition of FOXO1 and the p53 Signaling Pathway
title_short EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer via the Inhibition of FOXO1 and the p53 Signaling Pathway
title_sort ezh2-mediated microrna-375 upregulation promotes progression of breast cancer via the inhibition of foxo1 and the p53 signaling pathway
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041054/
https://www.ncbi.nlm.nih.gov/pubmed/33854524
http://dx.doi.org/10.3389/fgene.2021.633756
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