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http://purl.uniprot.org/citations/29126392http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29126392http://www.w3.org/2000/01/rdf-schema#comment"

Background

Triple-negative breast cancer (TNBC) is the malignancy with the worst outcome among all breast cancer subtypes. We reported that ETV1 is a significant oncogene in TNBC tumourigenesis. Consequently, investigating the critical regulatory microRNAs (miRNAs) of ETV1 may be beneficial for TNBC targeted therapy.

Methods

We performed in situ hybridization (ISH) and immunohistochemistry (IHC) to detect the location of miR-17-5p and ETV1 in TNBC patient samples, respectively. miR-17-5p expression in TNBC tissues and cell lines was assessed by quantitative real-time PCR (qRT-PCR). ETV1 expression was evaluated by qRT-PCR, western blotting and IHC. Cell Counting Kit-8 (CCK-8), colony formation, Transwell and wound closure assays were utilized to determine the TNBC cell proliferation and migration capabilities. In vivo tumour metastatic assays were performed in a zebra fish model.

Results

The abundance of miR-17-5p was significantly decreased in TNBC cell lines and clinical TNBC tissues. The miR-17-5p expression levels were closely correlated with tumour size (P < 0.05) and TNM stage (P < 0.05). By contrast, the expression of ETV1 was significantly up-regulated in TNBC cell lines and tissues. There is an inverse correlation between the expression status of miR-17-5p and ETV1 (r = -0.28, P = 3.88 × 10-3). Luciferase reporter assay confirmed that ETV1 was a direct target of miR-17-5p. Forced expression of miR-17-5p in MDA-MB-231 or BT549 cells significantly decreased ETV1 expression and suppressed cell proliferation, migration in vitro and tumour metastasis in vivo. However, rescuing the expression of ETV1 in the presence of miR-17-5p significantly recovered the cell phenotype. High miR-17-5p expression was associated with a significantly favourable prognosis, in either the ETV1-positive or ETV1-negative groups (log-rank test, P < 0.001; P < 0.001). Both univariate and multivariate analyses showed that miR-17-5p and ETV1 were independent risk factors in the prognosis of TNBC patient.

Conclusions

Our data indicate that miR-17-5p acts as a tumour suppressor in TNBC by targeting ETV1, and a low-abundance of miR-17-5p may be involved in the pathogenesis of TNBC. These findings indicate that miR-17-5p may be a therapeutic target for TNBC."xsd:string
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http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/author"Chen L."xsd:string
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/author"Liu Y."xsd:string
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/author"Li J."xsd:string
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/author"Lai Y."xsd:string
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/author"Ma J."xsd:string
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/author"Chang G."xsd:string
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/author"Wang S."xsd:string
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/author"Zhang L."xsd:string
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/author"Wang W."xsd:string
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/author"Bi J."xsd:string
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/author"Yao C."xsd:string
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/author"Ouyang M."xsd:string
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/author"Lv W."xsd:string
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/date"2017"xsd:gYear
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/name"BMC Cancer"xsd:string
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/pages"745"xsd:string
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/title"miR-17-5p suppresses cell proliferation and invasion by targeting ETV1 in triple-negative breast cancer."xsd:string
http://purl.uniprot.org/citations/29126392http://purl.uniprot.org/core/volume"17"xsd:string
http://purl.uniprot.org/citations/29126392http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/29126392
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