miR-3614-3p suppresses cell aggressiveness of human breast cancer by targeting AKT3 and HDAC1 expression

Background: MicroRNAs (miRNAs) regulate various pathophysiological functions and pathobiological progression in various cancers. Our recent study reported that miR-3614-3p significantly suppressed the proliferation of breast cancer (BC) cells by downregulating its host gene TRIM25. However, other functional roles of miR-3614-3p migration and invasion in BC and its potential mechanisms are not clearly elucidated.

Methods: In this study, we investigated miR-3614-3p regulation of AKT3 and HDAC1 expression in BC. miR-3614-3p and AKT3/HDAC1 mRNA expression levels were determined using quantitative real-time PCR (qRT-PCR) in MCF-7 and MDA-MB-231 BC cells. The effects of miR-3614-3p on migration and invasion were measured using wound healing and transwell migration assays. In BC cells, miR-3614-3p levels were remarkably low, and AKT3 and HDAC1 mRNA and protein levels were high as assessed by qRT-PCR and western blot. Finally, we investigated the role of AKT3/HDAC1 using silent interfering RNA (siRNA) and confirmed the targeting of AKT3 and HDAC1 3' UTR through miR-3614-3p using a luciferase reporter assay.

Results: In the present study, we found that overexpression of miR-3614-3p markedly suppressed tumor cell invasion and migration independent of TRIM25, whereas other target genes, AKT3 and HDAC1, were involved. Moreover, we found that the resulting silencing of AKT3 and HDAC1 suppressed cell migration.

Conclusions: miR-3614-3p is an anti-oncogene that can suppress BC cells by targeting AKT3 and HDAC1, revealing the potential role of miR-3614-3p in suppressing BC metastasis. Therefore, miR-3614 may act as a potential biomarker for BC prognosis.