microRNA-126-3p: Potential Player in Breast Cancer Tumorigenesis

Abstract

Background: Breast cancer (BC) is a major health burden that affects over one million women each year. It is the most prevalent cancer in women and number one cancer killer of them worldwide. BC is a heterogenous type of cancer composed of different subtypes characterized by distinct clinical outcomes. Thus, uncovering new players in breast cancer development might lead to better understanding of its tumorigenesis. During the past two decades, research has shed lights on microRNAs (miRNAs) as potential players in the development of several diseases including cancer. These small, noncoding RNA molecules are aberrantly expressed in breast cancer and play diverse roles in its tumorigenesis. Recently, our group has shown a panel of miRNA dysregulated in Lebanese BC tissues by conducting microarray profiling analysis. Of these miRNAs, miR-126-3p was significantly downregulated. Thus, our aim was to determine the role of miR-126-3p in BC progression.

Methods and Results: Downregulation of miR-126 in Lebanese BC tissues was validated using RT-qPCR. miR-126 levels were modulated in BC cell lines (MCF-7 and MDA-MB-231) and non-tumorigenic cell line (MCF-10A) by transfection with miR-126 mimic. MTT assay, PI analysis, and colony formation assay were done to determine the effect of overexpressing miR-126 on these cell lines. miR-126 had no effect on MCF-10A and MDA-MB-231 cell proliferation but, significantly decreased MCF-7 proliferation. No effect was detected on cell cycle progression whereas a trend towards a decrease was detected in the number of mammospheres upon transfection with miR-126 mimic. Then, in silico analysis was done to determine the potential targets of the corresponding miRNA. PLXNB2, SLC7A5, SPRED1, PLK2, HOXA9, MMP7, CRK, and IRS1 were selected as potential targets of miR-126. RT-qPCR data showed that miR-126 overexpression significantly downregulated SLC7A5 and PLXNB2 mRNA levels. Finally, in silico KM analysis was done to determine the correlation between miR-126 or SLC7A5 expression and overall survival (OS) of BC patients. Importantly, high expression of miR-126 or low expression of SLC7A5 correlated with better OS of ER+ patients.

Conclusion: Overall, our study suggests that miR-126 might play a tumor suppressor role in breast cancer through the modulation of different mRNA targets. However, further studies are required to validate its role. miR-126 might also be considered a potential prognostic biomarker in breast cancer.