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Cell Physiol Biochem. 2018;48(2):593-604. doi: 10.1159/000491888. Epub 2018 Jul 18.

MiR-4319 Suppress the Malignancy of Triple-Negative Breast Cancer by Regulating Self-Renewal and Tumorigenesis of Stem Cells.

Chu J1, Li Y1, Fan X2, Ma J2, Li J1, Lu G1, Zhang Y1, Huang Y3, Li W1, Huang X1, Fu Z1,2, Yin Y1,4, Yuan H2,5.

Author information

1
Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
2
Nanjing Maternal and Child Health Medical Institute, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China.
3
Department of Pharmacology and Chemical Biology, Magee Women's Research Institute, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
4
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China.
5
Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA.

Abstract

BACKGROUND/AIMS:

High levels of cancer stem cells (CSCs) in patients with triple-negative breast cancer (TNBC) correlate with risk of poor clinical outcome and possibly contribute to chemoresistance and metastasis in patients with highly malignant TNBC. Aberrant microRNA expression is associated with the dysfunction of self-renewal and proliferation in cancer stem cells, while there is little information about the TNBC-specific microRNAs in regulating CSC ability.

METHODS:

Solexa deep sequencing was performed to detect the expression levels of TNBC or non-TNBC stem cells (CSCs) microRNAs. Mammosphere formation assay, qRT-PCR and the xenograft model in nude mice were performed. Bioinformatic analysis and microarray were used to select the target gene, and luciferase reporter assays were used to confirm the binding sites.

RESULTS:

Solexa sequencing data exhibited differential expression of 193 microRNAs between TNBC and non-TNBC stem cells. The gene ontology analysis and pathways analyses showed that genes were involved in the maintenance of stemness. MiR-4319 could suppress the self-renewal and formation of tumorspheres in TNBC CSCs through E2F2, and also inhibited tumor initiation and metastasis in vivo. Moreover, increased E2F2 could reverse the effect of miR-4319 on the self-renewal in TNBC CSCs.

CONCLUSIONS:

MiR-4319 suppresses the malignancy of TNBC by regulating self-renewal and tumorigenesis of stem cells and might be a remarkable prognostic factor or therapeutic target for patients with TNBC.

KEYWORDS:

Cancer stem cell (CSC); E2F2; MiR-4319; Triple-Negative Breast Cancer

PMID:
30021199
DOI:
10.1159/000491888
[Indexed for MEDLINE]
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