Increased expression of miR-223-3p and miR-375-3p in HDL together with a high anti-inflammatory capacity of HDL in breast cancer

Background and Aims: HDL has anti-inflammatory actions and transports microRNAs that may be involved in the pathogenesis of breast cancer (BC). It was determined the expression of miRNAs and the anti-inflammatory activity of HDL isolated from newly diagnosed, naïve-treatment BC women (n=40) in comparison to age and body mass index paired control women (n=10). Methods: HDL was isolated from plasma by ultracentrifugation and its composition in lipids(total cholesterol, triglycerides, and phospholipids) was determined by enzymatic techniques, and apoA-I, by immunoturbidimetry. miRs were determined by RT-qPCR. Cholesterol-overloaded macrophages were incubated with HDL from BC and control women (24h).Then, cells were challenged with lipopolysaccharide (24h), and the secretion of interleukin6 (IL6) and tumor necrosis factor (TNF) were determined by ELISA. Comparisons were done by the Mann-Whitney and Kruskal-Wallis tests Results: HDL composition in lipids and apoA-I was similar between the control and BC groups. IL6 and TNF secretion were, respectively,47% (p=0.0009) and 34% (p=0.0378) lower in cells treated with HDL from BC as compared to controls, especially in advanced stages of BC (stages III and IV; p=<0.0001;58%) in comparison to initial stages (I and II; p=0.0095;35%). miR-17-5p, miR-138-1-3p, miR-223-3p, and miR-275-3p were found in the HDL particle but only miR-223-3p and miR-375-3p were, respectively, 5.6x (p=<0.0001) and 2.2x(p=0.0224) more expressed in HDL from BC presenting a high discriminating capacity with the control group (respectively, AUC=1.000; p=0.0003 and AUC=0.8105; p=0.0254) Conclusions: The increased anti-inflammatory capacity of HDL and differential expression of inflammation-related miRs in the HDL particle may contribute to BC pathophysiology and clinical outcome.