Exosome-derived miR-let-7c promotes angiogenesis in multiple myeloma by polarizing M2 macrophages in the bone marrow microenvironment

Leuk Res. 2021 Jun:105:106566. doi: 10.1016/j.leukres.2021.106566. Epub 2021 Mar 31.

Abstract

Angiogenesis is an integral part of the multiple myeloma (MM) microenvironment, and affects tumorigenesis, progression, invasion, and metastasis. Exosomes are essential for cell-cell communication and help in regulating the bone marrow microenvironment. Herein, we investigated macrophage polarization and angiogenesis in MM in vitro via exosome-derived miR-let-7c. We observed that exosomal miR-let-7c secreted by mesenchymal stem cells promoted M2 macrophage polarization, thereby enhancing angiogenesis in the bone marrow microenvironment. Suppressing miR-let-7c expression significantly inhibited vascular endothelial cell function in myeloma. Thus, exosomal miR-let-7c may be a reliable biomarker for early prediction of tumor progression and a promising therapeutic target for MM.

Keywords: Angiogenesis; Exosome; M2 macrophage; Myeloma; miR-let-7c.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Exosomes / genetics
  • Exosomes / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Macrophage Activation
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multiple Myeloma / genetics
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology*
  • Tumor Microenvironment / physiology

Substances

  • MIRNlet-7c microRNA, human
  • MicroRNAs