MicroRNA-200c and microRNA- 141 are regulated by a FOXP3-KAT2B axis and associated with tumor metastasis in breast cancer

Background Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory mechanisms remain elusive. Methods We investigated FOXP3 -inducible breast cancer cells, Foxp3 heterozygous Scurfy mutant ( Foxp3 sf/+ ) female mice,...

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Published inBreast cancer research : BCR Vol. 19; no. 1; pp. 73 - 13
Main Authors Zhang, Guangxin, Zhang, Wei, Li, Bingjin, Stringer-Reasor, Erica, Chu, Chengjing, Sun, Liyan, Bae, Sejong, Chen, Dongquan, Wei, Shi, Jiao, Kenneth, Yang, Wei-Hsiung, Cui, Ranji, Liu, Runhua, Wang, Lizhong
Format Journal Article
LanguageEnglish
Published London BioMed Central 21.06.2017
BioMed Central Ltd
BMC
Subjects
Adult
Aged
Animals
Benign
Biomarkers
Biomarkers, Tumor
Biomedical and Life Sciences
Biomedicine
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cancer metastasis
Cancer Research
Cell Line, Tumor
Circulating MicroRNA
Circulation
Development and progression
Disease Models, Animal
Disease Progression
Epithelial cells
Exosome
Female
Forkhead Transcription Factors - genetics
FOXP3
Foxp3 protein
Gene expression
Gene Expression Regulation, Neoplastic
Genetic aspects
Human subjects
Humans
Lungs
Lymphatic system
Metastases
Metastasis
Mice
MicroRNA
MicroRNAs
MicroRNAs - genetics
Middle Aged
miRNA
Mutation
Neoplasm Grading
Neoplasm Metastasis
Neoplasm Staging
Oncology
p300-CBP Transcription Factors - genetics
Plasma levels
Research Article
ROC Curve
Rodents
Surgical Oncology
Transcription, Genetic
Tumor cells
Tumor metastasis
Tumors
Womens health
United States > US
microRNA
Breast cancer
Exosome
FOXP3
Circulation
Tumor metastasis
Online AccessGet full text
ISSN1465-542X
1465-5411
1465-542X
DOI10.1186/s13058-017-0858-x

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Abstract Background Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory mechanisms remain elusive. Methods We investigated FOXP3 -inducible breast cancer cells, Foxp3 heterozygous Scurfy mutant ( Foxp3 sf/+ ) female mice, and patients with breast cancer for characterization of the formation and regulation of the miR-200 family in breast cancer cells and circulation. Participants (259), including patients with breast cancer or benign breast tumors, members of breast cancer families, and healthy controls, were assessed for tumor and circulating levels of the miR-200 family. Results First, we identified a FOXP3-KAT2B-miR-200c/141 axis in breast cancer cells. Second, aging Foxp3 sf/+ female mice developed spontaneous breast cancers and lung metastases. Levels of miR-200c and miR-141 were lower in Foxp3 sf/+ tumor cells than in normal breast epithelial cells, but plasma levels of miR-200c and miR-141 in the Foxp3 sf/+ mice increased during tumor progression and metastasis. Third, in patients with breast cancer, the levels of miR-200c and 141 were lower in FOXP3 low relative to those with FOXP3 high breast cancer cells, especially in late-stage and metastatic cancer cells. The levels of miR-200c and miR-141 were higher in plasma from patients with metastatic breast cancer than in plasma from those with localized breast cancer, with benign breast tumors, with a family history of breast cancer, or from healthy controls. Finally, in Foxp3 sf/+ mice, plasma miR-200c and miR-141 appeared to be released from tumor cells. Conclusions miR-200c and miR-141 are regulated by a FOXP3-KAT2B axis in breast cancer cells, and circulating levels of miR-200c and miR-141 are potential biomarkers for early detection of breast cancer metastases.
AbstractList Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory mechanisms remain elusive.BACKGROUNDMembers of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory mechanisms remain elusive.We investigated FOXP3-inducible breast cancer cells, Foxp3 heterozygous Scurfy mutant (Foxp3 sf/+ ) female mice, and patients with breast cancer for characterization of the formation and regulation of the miR-200 family in breast cancer cells and circulation. Participants (259), including patients with breast cancer or benign breast tumors, members of breast cancer families, and healthy controls, were assessed for tumor and circulating levels of the miR-200 family.METHODSWe investigated FOXP3-inducible breast cancer cells, Foxp3 heterozygous Scurfy mutant (Foxp3 sf/+ ) female mice, and patients with breast cancer for characterization of the formation and regulation of the miR-200 family in breast cancer cells and circulation. Participants (259), including patients with breast cancer or benign breast tumors, members of breast cancer families, and healthy controls, were assessed for tumor and circulating levels of the miR-200 family.First, we identified a FOXP3-KAT2B-miR-200c/141 axis in breast cancer cells. Second, aging Foxp3 sf/+ female mice developed spontaneous breast cancers and lung metastases. Levels of miR-200c and miR-141 were lower in Foxp3 sf/+ tumor cells than in normal breast epithelial cells, but plasma levels of miR-200c and miR-141 in the Foxp3 sf/+ mice increased during tumor progression and metastasis. Third, in patients with breast cancer, the levels of miR-200c and 141 were lower in FOXP3 low relative to those with FOXP3 high breast cancer cells, especially in late-stage and metastatic cancer cells. The levels of miR-200c and miR-141 were higher in plasma from patients with metastatic breast cancer than in plasma from those with localized breast cancer, with benign breast tumors, with a family history of breast cancer, or from healthy controls. Finally, in Foxp3 sf/+ mice, plasma miR-200c and miR-141 appeared to be released from tumor cells.RESULTSFirst, we identified a FOXP3-KAT2B-miR-200c/141 axis in breast cancer cells. Second, aging Foxp3 sf/+ female mice developed spontaneous breast cancers and lung metastases. Levels of miR-200c and miR-141 were lower in Foxp3 sf/+ tumor cells than in normal breast epithelial cells, but plasma levels of miR-200c and miR-141 in the Foxp3 sf/+ mice increased during tumor progression and metastasis. Third, in patients with breast cancer, the levels of miR-200c and 141 were lower in FOXP3 low relative to those with FOXP3 high breast cancer cells, especially in late-stage and metastatic cancer cells. The levels of miR-200c and miR-141 were higher in plasma from patients with metastatic breast cancer than in plasma from those with localized breast cancer, with benign breast tumors, with a family history of breast cancer, or from healthy controls. Finally, in Foxp3 sf/+ mice, plasma miR-200c and miR-141 appeared to be released from tumor cells.miR-200c and miR-141 are regulated by a FOXP3-KAT2B axis in breast cancer cells, and circulating levels of miR-200c and miR-141 are potential biomarkers for early detection of breast cancer metastases.CONCLUSIONSmiR-200c and miR-141 are regulated by a FOXP3-KAT2B axis in breast cancer cells, and circulating levels of miR-200c and miR-141 are potential biomarkers for early detection of breast cancer metastases.
Abstract Background Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory mechanisms remain elusive. Methods We investigated FOXP3-inducible breast cancer cells, Foxp3 heterozygous Scurfy mutant (Foxp3 sf/+ ) female mice, and patients with breast cancer for characterization of the formation and regulation of the miR-200 family in breast cancer cells and circulation. Participants (259), including patients with breast cancer or benign breast tumors, members of breast cancer families, and healthy controls, were assessed for tumor and circulating levels of the miR-200 family. Results First, we identified a FOXP3-KAT2B-miR-200c/141 axis in breast cancer cells. Second, aging Foxp3 sf/+ female mice developed spontaneous breast cancers and lung metastases. Levels of miR-200c and miR-141 were lower in Foxp3 sf/+ tumor cells than in normal breast epithelial cells, but plasma levels of miR-200c and miR-141 in the Foxp3 sf/+ mice increased during tumor progression and metastasis. Third, in patients with breast cancer, the levels of miR-200c and 141 were lower in FOXP3 low relative to those with FOXP3 high breast cancer cells, especially in late-stage and metastatic cancer cells. The levels of miR-200c and miR-141 were higher in plasma from patients with metastatic breast cancer than in plasma from those with localized breast cancer, with benign breast tumors, with a family history of breast cancer, or from healthy controls. Finally, in Foxp3 sf/+ mice, plasma miR-200c and miR-141 appeared to be released from tumor cells. Conclusions miR-200c and miR-141 are regulated by a FOXP3-KAT2B axis in breast cancer cells, and circulating levels of miR-200c and miR-141 are potential biomarkers for early detection of breast cancer metastases.
Background Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory mechanisms remain elusive. Methods We investigated FOXP3 -inducible breast cancer cells, Foxp3 heterozygous Scurfy mutant ( Foxp3 sf/+ ) female mice, and patients with breast cancer for characterization of the formation and regulation of the miR-200 family in breast cancer cells and circulation. Participants (259), including patients with breast cancer or benign breast tumors, members of breast cancer families, and healthy controls, were assessed for tumor and circulating levels of the miR-200 family. Results First, we identified a FOXP3-KAT2B-miR-200c/141 axis in breast cancer cells. Second, aging Foxp3 sf/+ female mice developed spontaneous breast cancers and lung metastases. Levels of miR-200c and miR-141 were lower in Foxp3 sf/+ tumor cells than in normal breast epithelial cells, but plasma levels of miR-200c and miR-141 in the Foxp3 sf/+ mice increased during tumor progression and metastasis. Third, in patients with breast cancer, the levels of miR-200c and 141 were lower in FOXP3 low relative to those with FOXP3 high breast cancer cells, especially in late-stage and metastatic cancer cells. The levels of miR-200c and miR-141 were higher in plasma from patients with metastatic breast cancer than in plasma from those with localized breast cancer, with benign breast tumors, with a family history of breast cancer, or from healthy controls. Finally, in Foxp3 sf/+ mice, plasma miR-200c and miR-141 appeared to be released from tumor cells. Conclusions miR-200c and miR-141 are regulated by a FOXP3-KAT2B axis in breast cancer cells, and circulating levels of miR-200c and miR-141 are potential biomarkers for early detection of breast cancer metastases.
Background Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory mechanisms remain elusive. Methods We investigated FOXP3-inducible breast cancer cells, Foxp3 heterozygous Scurfy mutant (Foxp3 sf/+ ) female mice, and patients with breast cancer for characterization of the formation and regulation of the miR-200 family in breast cancer cells and circulation. Participants (259), including patients with breast cancer or benign breast tumors, members of breast cancer families, and healthy controls, were assessed for tumor and circulating levels of the miR-200 family. Results First, we identified a FOXP3-KAT2B-miR-200c/141 axis in breast cancer cells. Second, aging Foxp3 sf/+ female mice developed spontaneous breast cancers and lung metastases. Levels of miR-200c and miR-141 were lower in Foxp3 sf/+ tumor cells than in normal breast epithelial cells, but plasma levels of miR-200c and miR-141 in the Foxp3 sf/+ mice increased during tumor progression and metastasis. Third, in patients with breast cancer, the levels of miR-200c and 141 were lower in FOXP3 low relative to those with FOXP3 high breast cancer cells, especially in late-stage and metastatic cancer cells. The levels of miR-200c and miR-141 were higher in plasma from patients with metastatic breast cancer than in plasma from those with localized breast cancer, with benign breast tumors, with a family history of breast cancer, or from healthy controls. Finally, in Foxp3 sf/+ mice, plasma miR-200c and miR-141 appeared to be released from tumor cells. Conclusions miR-200c and miR-141 are regulated by a FOXP3-KAT2B axis in breast cancer cells, and circulating levels of miR-200c and miR-141 are potential biomarkers for early detection of breast cancer metastases.
Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory mechanisms remain elusive. We investigated FOXP3-inducible breast cancer cells, Foxp3 heterozygous Scurfy mutant (Foxp3 ) female mice, and patients with breast cancer for characterization of the formation and regulation of the miR-200 family in breast cancer cells and circulation. Participants (259), including patients with breast cancer or benign breast tumors, members of breast cancer families, and healthy controls, were assessed for tumor and circulating levels of the miR-200 family. First, we identified a FOXP3-KAT2B-miR-200c/141 axis in breast cancer cells. Second, aging Foxp3 female mice developed spontaneous breast cancers and lung metastases. Levels of miR-200c and miR-141 were lower in Foxp3 tumor cells than in normal breast epithelial cells, but plasma levels of miR-200c and miR-141 in the Foxp3 mice increased during tumor progression and metastasis. Third, in patients with breast cancer, the levels of miR-200c and 141 were lower in FOXP3 relative to those with FOXP3 breast cancer cells, especially in late-stage and metastatic cancer cells. The levels of miR-200c and miR-141 were higher in plasma from patients with metastatic breast cancer than in plasma from those with localized breast cancer, with benign breast tumors, with a family history of breast cancer, or from healthy controls. Finally, in Foxp3 mice, plasma miR-200c and miR-141 appeared to be released from tumor cells. miR-200c and miR-141 are regulated by a FOXP3-KAT2B axis in breast cancer cells, and circulating levels of miR-200c and miR-141 are potential biomarkers for early detection of breast cancer metastases.
Background Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory mechanisms remain elusive. Methods We investigated FOXP3-inducible breast cancer cells, Foxp3 heterozygous Scurfy mutant (Foxp3.sup.sf/+) female mice, and patients with breast cancer for characterization of the formation and regulation of the miR-200 family in breast cancer cells and circulation. Participants (259), including patients with breast cancer or benign breast tumors, members of breast cancer families, and healthy controls, were assessed for tumor and circulating levels of the miR-200 family. Results First, we identified a FOXP3-KAT2B-miR-200c/141 axis in breast cancer cells. Second, aging Foxp3.sup.sf/+ female mice developed spontaneous breast cancers and lung metastases. Levels of miR-200c and miR-141 were lower in Foxp3.sup.sf/+ tumor cells than in normal breast epithelial cells, but plasma levels of miR-200c and miR-141 in the Foxp3.sup.sf/+ mice increased during tumor progression and metastasis. Third, in patients with breast cancer, the levels of miR-200c and 141 were lower in FOXP3.sup.low relative to those with FOXP3.sup.high breast cancer cells, especially in late-stage and metastatic cancer cells. The levels of miR-200c and miR-141 were higher in plasma from patients with metastatic breast cancer than in plasma from those with localized breast cancer, with benign breast tumors, with a family history of breast cancer, or from healthy controls. Finally, in Foxp3.sup.sf/+ mice, plasma miR-200c and miR-141 appeared to be released from tumor cells. Conclusions miR-200c and miR-141 are regulated by a FOXP3-KAT2B axis in breast cancer cells, and circulating levels of miR-200c and miR-141 are potential biomarkers for early detection of breast cancer metastases. Keywords: microRNA, FOXP3, Breast cancer, Tumor metastasis, Circulation, Exosome
Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory mechanisms remain elusive. We investigated FOXP3-inducible breast cancer cells, Foxp3 heterozygous Scurfy mutant (Foxp3.sup.sf/+) female mice, and patients with breast cancer for characterization of the formation and regulation of the miR-200 family in breast cancer cells and circulation. Participants (259), including patients with breast cancer or benign breast tumors, members of breast cancer families, and healthy controls, were assessed for tumor and circulating levels of the miR-200 family. First, we identified a FOXP3-KAT2B-miR-200c/141 axis in breast cancer cells. Second, aging Foxp3.sup.sf/+ female mice developed spontaneous breast cancers and lung metastases. Levels of miR-200c and miR-141 were lower in Foxp3.sup.sf/+ tumor cells than in normal breast epithelial cells, but plasma levels of miR-200c and miR-141 in the Foxp3.sup.sf/+ mice increased during tumor progression and metastasis. Third, in patients with breast cancer, the levels of miR-200c and 141 were lower in FOXP3.sup.low relative to those with FOXP3.sup.high breast cancer cells, especially in late-stage and metastatic cancer cells. The levels of miR-200c and miR-141 were higher in plasma from patients with metastatic breast cancer than in plasma from those with localized breast cancer, with benign breast tumors, with a family history of breast cancer, or from healthy controls. Finally, in Foxp3.sup.sf/+ mice, plasma miR-200c and miR-141 appeared to be released from tumor cells. miR-200c and miR-141 are regulated by a FOXP3-KAT2B axis in breast cancer cells, and circulating levels of miR-200c and miR-141 are potential biomarkers for early detection of breast cancer metastases.
ArticleNumber 73
Audience Academic
Author Wei, Shi
Bae, Sejong
Zhang, Wei
Cui, Ranji
Zhang, Guangxin
Sun, Liyan
Li, Bingjin
Jiao, Kenneth
Liu, Runhua
Chu, Chengjing
Stringer-Reasor, Erica
Wang, Lizhong
Chen, Dongquan
Yang, Wei-Hsiung
Author_xml – sequence: 1
  givenname: Guangxin
  surname: Zhang
  fullname: Zhang, Guangxin
  organization: Provincial Key Laboratory on Molecular and Chemical Genetic, The Second Hospital of Jilin University, Department of Genetics, University of Alabama at Birmingham
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  givenname: Wei
  surname: Zhang
  fullname: Zhang, Wei
  organization: Chinese Center for Endemic Disease Control, Harbin Medical University
– sequence: 3
  givenname: Bingjin
  surname: Li
  fullname: Li, Bingjin
  organization: Provincial Key Laboratory on Molecular and Chemical Genetic, The Second Hospital of Jilin University
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  givenname: Erica
  surname: Stringer-Reasor
  fullname: Stringer-Reasor, Erica
  organization: Hematology/Oncology Section, Department of Medicine, University of Alabama at Birmingham
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  givenname: Chengjing
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  fullname: Chu, Chengjing
  organization: Department of Applied Psychology, Humanities and Management Colleges, Guangdong Medical University
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  surname: Sun
  fullname: Sun, Liyan
  organization: Chinese Center for Endemic Disease Control, Harbin Medical University
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  givenname: Sejong
  surname: Bae
  fullname: Bae, Sejong
  organization: Division of Preventive Medicine, University of Alabama at Birmingham
– sequence: 8
  givenname: Dongquan
  surname: Chen
  fullname: Chen, Dongquan
  organization: Division of Preventive Medicine, University of Alabama at Birmingham
– sequence: 9
  givenname: Shi
  surname: Wei
  fullname: Wei, Shi
  organization: Department of Pathology, University of Alabama at Birmingham
– sequence: 10
  givenname: Kenneth
  surname: Jiao
  fullname: Jiao, Kenneth
  organization: Comprehensive Cancer Center, University of Alabama at Birmingham
– sequence: 11
  givenname: Wei-Hsiung
  surname: Yang
  fullname: Yang, Wei-Hsiung
  organization: Department of Biomedical Sciences, Mercer University
– sequence: 12
  givenname: Ranji
  surname: Cui
  fullname: Cui, Ranji
  email: cuiranji@jlu.edu.cn
  organization: Provincial Key Laboratory on Molecular and Chemical Genetic, The Second Hospital of Jilin University
– sequence: 13
  givenname: Runhua
  surname: Liu
  fullname: Liu, Runhua
  email: runhua@uab.edu
  organization: Department of Genetics, University of Alabama at Birmingham, Comprehensive Cancer Center, University of Alabama at Birmingham
– sequence: 14
  givenname: Lizhong
  orcidid: 0000-0003-1980-4730
  surname: Wang
  fullname: Wang, Lizhong
  email: lwang12@uab.edu
  organization: Department of Genetics, University of Alabama at Birmingham, Comprehensive Cancer Center, University of Alabama at Birmingham
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28637482$$D View this record in MEDLINE/PubMed
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Issue 1
Keywords microRNA
Breast cancer
Exosome
FOXP3
Circulation
Tumor metastasis
Language English
License Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.
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– volume: 44
  start-page: 770
  issue: 5
  year: 2011
  ident: 858_CR30
  publication-title: Mol Cell
  doi: 10.1016/j.molcel.2011.10.012
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Snippet Background Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory...
Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory mechanisms remain...
Background Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory...
Abstract Background Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory...
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SubjectTerms Adult
Aged
Animals
Benign
Biomarkers
Biomarkers, Tumor
Biomedical and Life Sciences
Biomedicine
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cancer metastasis
Cancer Research
Cell Line, Tumor
Circulating MicroRNA
Circulation
Development and progression
Disease Models, Animal
Disease Progression
Epithelial cells
Exosome
Female
Forkhead Transcription Factors - genetics
FOXP3
Foxp3 protein
Gene expression
Gene Expression Regulation, Neoplastic
Genetic aspects
Human subjects
Humans
Lungs
Lymphatic system
Metastases
Metastasis
Mice
MicroRNA
MicroRNAs
MicroRNAs - genetics
Middle Aged
miRNA
Mutation
Neoplasm Grading
Neoplasm Metastasis
Neoplasm Staging
Oncology
p300-CBP Transcription Factors - genetics
Plasma levels
Research Article
ROC Curve
Rodents
Surgical Oncology
Transcription, Genetic
Tumor cells
Tumor metastasis
Tumors
Womens health
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Title MicroRNA-200c and microRNA- 141 are regulated by a FOXP3-KAT2B axis and associated with tumor metastasis in breast cancer
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