期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 48, 期 2, 页码 593-604出版社
KARGER
DOI: 10.1159/000491888
关键词
Triple-Negative Breast Cancer; MiR-4319; E2F2; Cancer stem cell (CSC)
资金
- National Natural Science Foundation of China [81172503, 81302304, 81572603, 81570804]
- Key projects of Jiangsu Health Department [RC201153]
- Second Level of 333 Project of Jiangsu Province [BRA2017534]
- Third Level of 333 Project of Jiangsu Province [BRA2015470]
- Project of Jiangsu Provincial Medical Talent [ZDRCA2016023]
- Project of Jiangsu Provincial Medical youth Talent [QNRC2016095]
- General Project of Nanjing Health Bureau [YKK17179]
- Wu Jieping Medical Foundation [320.6750.17006]
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. (c) 2018 The Author(s) Published by S. Karger AG, Basel
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