MiR-25-3p promotes the proliferation of triple negative breast cancer by targeting BTG2

Hua Chen,Hong Pan,Xiaoan Liu,Wenbin Zhou,Yi Qian

doi:10.1186/s12943-017-0754-0

Hua Chen, Hong Pan + Show 3 more

Open Access

https://doi.org/10.1186/s12943-017-0754-0

Copy DOI

Abstract

BackgroundTriple-negative breast cancer (TNBC) is highly invasive and aggressive and lacks specific molecular targets to improve the prognosis. MiR-25-3p promotes proliferation of many tumors and its role and underlying mechanisms in TNBC remain to be well elucidated.MethodsDifferential expression of miR-25-3p in TNBC was measured with quantitative real-time PCR (qRT-PCR) in both TNBC tissues and cell lines and was validated in the Cancer Genome Atlas (TCGA) database. The effects of miR-25-3p on proliferation, apoptosis capacity of TNBC were evaluated using Cell counting kit-8 (CCK-8), colony formation assay and Annexin V-FITC/PI analyses. The tumor growth in vivo was observed in xenograft model. Luciferase reporter assay, qPCR and western blot were performed to validate a potential target of miR-25-3p in TNBC. Involvement of the AKT and MAPK pathways was investigated by western blot.ResultsMiR-25-3p was found to be upregulated in TNBC in tissues and cell lines. MiR-25-3p promoted TNBC cell proliferation in vitro and tumor growth in xenograft model, while suppression of miR-25-3p induced cell apoptosis. The luciferase reporter assay confirmed that B-cell translocation gene 2 (BTG2) might be a direct target of miR-25-3p, and its expression was negatively regulated by miR-25-3p. Moreover, inhibition of BTG2 expression accounted for the role of miR-25-3p in TNBC. Furthermore, BTG2 suppression might indirectly activate the AKT and ERK-MAPK signaling pathways to mediate the downstream effects of miR-25-3p.ConclusionsThis study demonstrates that miR-25-3p promotes proliferation by targeting tumor suppressor BTG2 and may identify new diagnostic and therapeutic targets in TNBC.

Highlights

Triple-negative breast cancer (TNBC) is highly invasive and aggressive and lacks specific molecular targets to improve the prognosis
MiR-25-3p is over-expressed in both TNBC tissue samples and cell lines To identify differentially expressed miRNAs in TNBC, we performed miRNA microarray assay to examine the miRNA expression profiles of five paired samples of TNBC and adjacent normal tissues
The expression level of miR-25-3p was further examined in 20 pairs of TNBC tissues and adjacent normal tissues, including luminal cell lines by quantitative real-time PCR, and was found to be significantly increased in TNBC tissues (Fig. 1c)

Summary

Introduction

Triple-negative breast cancer (TNBC) is highly invasive and aggressive and lacks specific molecular targets to improve the prognosis. MiR-25-3p promotes proliferation of many tumors and its role and underlying mechanisms in TNBC remain to be well elucidated. According to the expression status of hormone receptors and human epidermal growth factor receptor-2 (HER2), breast cancer consists of luminal A-like, luminal B-like, HER2-positive and triple-negative molecular subtypes respectively [2]. Triple-negative breast cancer (TNBC) is defined as the subtype lacking expression of estrogen and progesterone receptors (ER and PR) and HER2, and is highly invasive. MicroRNAs regulate gene expression via binding to the 3’untranslated region (3’UTR) of the target mRNAs resulting in post-transcriptional repression or degradation [5]. MiRNAs play important roles in a series of tumor biological processes, including tumor proliferation, differentiation, apoptosis, migration and invasion [6].

Methods

Results

Conclusion