Platelet-derived microvesicles isolated from type-2 diabetes mellitus patients harbour an altered miRNA signature and drive MDA-MB-231 triple-negative breast cancer cell invasion

The underlying causes of breast cancer are diverse, however, there is a striking association between type 2 diabetes (T2DM) and poor patient outcomes. Platelets become activated in both T2DM and breast cancer patients and have been implicated in tumorigenesis through a multitude of pathways. Here transcriptomic analysis of T2DM-patient derived PMVs revealed an altered micro-RNA (miRNA) signature compared with normoglycaemic control patients. Interestingly, interrogation of these data identifies a shift towards an oncogenic signature in T2DM-derived PMVs, with increased levels of several miRNA implicated in breast cancer progression and poor prognosis. Functional studies demonstrate that PMVs isolated from T2DM patient blood are internalised by triple-negative breast cancer (TNBC) cells in vitro, and that co-incubation with T2DM-patient derived PMVs led to significantly increased TNBC cell invasion compared with PMVs from healthy volunteers. Together, these data suggest that circulating PMVs in T2DM patients may contribute to the progression of TNBC. Overall design: To investigate the role of T2DM-derived PMV miRNA signature on the risk of breast cancer progression in diabetic patients, we extracted PMV RNA from healthy young adult volunteers (n=8) and T2DM patients with HbA1C>50 (n=4). We then prepared small RNA-Seq libraries using NEBNext® Ultra™ DNA Library Prep Kit for Illumina® (NEB, UK) and analysed the samples using via NextSeq 500. Differential miRNA expression analysis was performed between diabetic (D) and non-diabetic (C) samples.