miR-17-5p suppresses cell proliferation and invasion by targeting ETV1 in triple-negative breast cancer

Abstract

BackgroundTriple-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.MethodsWe 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.ResultsThe 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3674-x) contains supplementary material, which is available to authorized users.

Prognostic Value and Potential Regulatory Mechanism of Alternative Splicing in Geriatric Breast Cancer

“…In the ES model, we analyzed 14 AS events related to the prognosis of GBC, including ETV1, SH2D4A, BCLAF1, and SUV420H1. One breast cancer study indicated that cell proliferation and invasion in triple-negative breast cancer can be suppressed through miR-17-5p targeting ETV1, and ETV1 was proven to be a significant oncogene in triple-negative breast cancer [53]. This is also consistent with our findings; the overexpression of ETV1 is associated with poor prognosis.…”

Silencing of miR-17-5p suppresses cell proliferation and promotes cell apoptosis by directly targeting PIK3R1 in laryngeal squamous cell carcinoma

“…Furthermore, miR-1297, miR-143-3p, miR-503 and miR-205 also promote LSCC cell progression [14][15][16][17]. Recent studies have confirmed that miR-17-5p plays critical roles in tumor progression, such as pancreatic cancer, breast cancer, hepatocellular carcinoma, gastric cancer and prostate cancer [18][19][20][21][22]. However, the expression and biological functions of miR-17-5p in LSCC remain unclear.…”

Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer

“…We further analyzed whether any of the highly expressed miRNAs were previously associated with TNBC and found that seven out of the 83 miRNAs, common for all three cell lines (miR-181b-5p, miR-221-3p, miR-27a-3p, miR-21-3p, miR-20a-5p, miR-103a-3p and miR-25-3p), have been previously associated with the TNBC phenotype [39][40][41][42][43][44][45][46][47] Another three molecules, miR-210-3p, miR-155-5p and miR-125b-5p, highly expressed in HCC1806 and Hs 578T cells, are known as hallmarks of TNBC [40,41,48,49], whereas miR-342-3p, highly expressed exclusively in basal-like TNBC cell lines, has been previously described as an important regulator of molecular mechanisms of this breast cancer subtype [50]. Interestingly, miRNAs miR-101-3p, miR-17-5p, miR-93-5p, miR-340-5p, and miR-31-5p, known mainly for their tumor suppressor properties, were found among the top expressed miRNAs in our dataset [51][52][53][54][55][56][57][58]. Finally, three miRNAs whose role is contradictory according to the literature (miR-181a-5p, miR-182-5p, and miR-26a-5p) were found to be highly expressed in all three cell lines analyzed [39,[59][60][61][62][63][64][65][66][67][68].…”