Down-regulation of miR-129-5p via the Twist1-Snail feedback loop stimulates the epithelial-mesenchymal transition and is associated with poor prognosis in breast cancer

Yue Yu; Ying Zhao; Xiao-Hu Sun; Jie Ge; Bin Zhang; Xin Wang; Xu-Chen Cao

doi:10.18632/oncotarget.5406

Down-regulation of miR-129-5p via the Twist1-Snail feedback loop stimulates the epithelial-mesenchymal transition and is associated with poor prognosis in breast cancer

Oncotarget. 2015 Oct 27;6(33):34423-36. doi: 10.18632/oncotarget.5406.

Authors

Yue Yu^{1

2

3}, Ying Zhao^{1

2

3}, Xiao-Hu Sun^{1

2

3}, Jie Ge^{1

2

3}, Bin Zhang^{1

2

3}, Xin Wang^{1

2

3}, Xu-Chen Cao^{1

2

3}

Affiliations

¹ The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.
² Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
³ Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin 300060, China.

Abstract

The epithelial to mesenchymal transition (EMT) plays a pivotal role in breast cancer progression. We found that overexpression of miR-129-5p reversed EMT, whereas depletion of miR-129-5p induced EMT in breast cancer cells. We demonstrated that Twist1 is a direct target of miR-129-5p. Both Twist1 and Snail transcriptionally suppressed miR-129-5p expression. Levels of miR-129-5p were low in breast cancer tissues. miR-129-5p down-regulation correlated with advanced clinical stage and poor prognosis in patients with breast cancer. miR-129-5p expression negatively correlated with Twist1 and Snail expression. Thus, miR-129-5p down-regulation fosters EMT in breast cancer by increasing Twist1-Snail and activating a negative feedback loop.

Keywords: EMT; Snail; Twist1; breast cancer progression; miR-129-5p.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Breast Neoplasms / genetics
Breast Neoplasms / mortality
Breast Neoplasms / pathology*
Cell Line, Tumor
Chromatin Immunoprecipitation
Down-Regulation
Epithelial-Mesenchymal Transition / genetics*
Feedback, Physiological
Female
Fluorescent Antibody Technique
Gene Expression Regulation, Neoplastic / genetics
Genes, Tumor Suppressor
Humans
Immunoblotting
Kaplan-Meier Estimate
MicroRNAs / biosynthesis*
MicroRNAs / genetics
Middle Aged
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Prognosis
RNA, Small Interfering
Reverse Transcriptase Polymerase Chain Reaction
Snail Family Transcription Factors
Transcription Factors / genetics
Transcription Factors / metabolism*
Transfection
Twist-Related Protein 1 / genetics
Twist-Related Protein 1 / metabolism*

Substances

MicroRNAs
Mirn129 microRNA, human
Nuclear Proteins
RNA, Small Interfering
Snail Family Transcription Factors
TWIST1 protein, human
Transcription Factors
Twist-Related Protein 1