PLoS ONE (Jan 2024)

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.

  • Anca Tutuianu,
  • Chinedu A Anene,
  • Mikayla Shelton,
  • Valerie Speirs,
  • Donald C Whitelaw,
  • Joanne Thorpe,
  • Wayne Roberts,
  • James R Boyne

DOI
https://doi.org/10.1371/journal.pone.0304870
Journal volume & issue
Vol. 19, no. 6
p. e0304870

Abstract

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The underlying causes of breast cancer are diverse, however, there is a striking association between type 2 diabetes and poor patient outcomes. Platelet activation is a common feature of both type 2 diabetes and breast cancer and has been implicated in tumourigenesis through a multitude of pathways. Here transcriptomic analysis of type 2 diabetes patient-derived platelet microvesicles revealed an altered miRNA signature compared with normoglycaemic control patients. Interestingly, interrogation of these data identifies a shift towards an oncogenic signature in type 2 diabetes-derived platelet microvesicles, with increased levels of miRNAs implicated in breast cancer progression and poor prognosis. Functional studies demonstrate that platelet microvesicles isolated from type 2 diabetes patient blood are internalised by triple-negative breast cancer cells in vitro, and that co-incubation with type 2 diabetes patient-derived platelet microvesicles led to significantly increased expression of epithelial to mesenchymal transition markers and triple-negative breast cancer cell invasion compared with platelet microvesicles from healthy volunteers. Together, these data suggest that circulating PMVs in type 2 diabetes patients may contribute to the progression of triple-negative breast cancer.