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

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.Electronic supplementary materialThe online version of this article (10.1186/s12943-017-0754-0) contains supplementary material, which is available to authorized users.

Sevoflurane inhibits the proliferation and invasion of hepatocellular carcinoma cells through regulating the PTEN/Akt/GSK‑3β/β‑catenin signaling pathway by downregulating miR‑25‑3p

“…These findings suggest that miRNAs could become novel molecular targets for HCC treatment. The oncogenic roles of miR-25-3p in numerous types of cancers have previously been investigated (40,41). In HCC, one previous study demonstrated that miR-25-3p was upregulated in HCC tissues when compared with adjacent normal tissues and that the upregulation of miR-25-3p is of predictive value on poor prognosis (22).…”

<p>Upregulation Of miR-153 Inhibits Triple-Negative Breast Cancer Progression By Targeting ZEB2-Mediated EMT And Contributes To Better Prognosis</p>

“…However, emerging studies have confirmed that different miRNAs play diverse roles in TNBC, some as tumorigenic agents, and some as tumor inhibitors. For example, as tumorigenic agents, miR-25, 16 miR-20, 17 miR-224, 18 miR-135 19 and miR-301 20 promote the occurrence and development of TNBC, whereas miR-124, 15 miR-4417, 21 miR-4306, 22 miR-199, 23 miR-1287 24 and miR-3178 25 as tumor inhibitors inhibit the oncogenesis and development of TNBC. In this study, relative miR-153 expression in TNBC tissues and cells was remarkably lower than that in corresponding adjacent noncancerous tissues and normal breast epithelial cells.…”

MicroRNAs Involved in Carcinogenesis, Prognosis, Therapeutic Resistance, and Applications in Human Triple-Negative Breast Cancer

“…Besides, other panels of upregulated miRNAs, such as miR-20a-5p, miR-25-3p, miR-135b, and miR-502, are associated with the proliferation of TNBC and cell lines by targeting different genes. The expression of B-cell translocation gene 2 (BTG2) is negatively regulated by miR-25-3p, and indirectly activates the AKT and ERK-mitogen-activated protein kinase (MAPK) signaling pathways to mediate the proliferation of TNBC cell [148]. MiR-20a-5p promotes TNBC cell proliferation by targeting the Runt-related transcription factor 3 (RUNX3), as well as its direct downstream targets, Bim and p21 [149].…”