Mesenchymal stem cells-originated exosomal microRNA-152 impairs proliferation, invasion and migration of thyroid carcinoma cells by interacting with DPP4

J Endocrinol Invest. 2020 Dec;43(12):1787-1796. doi: 10.1007/s40618-020-01406-2. Epub 2020 Sep 2.

Abstract

Background: Thyroid carcinoma (THCA) is the most prevalent tumor in the endocrine system with an increasing incidence. Recent studies have underscored the function of microRNAs (miRNAs) in THCA. Nevertheless, knowledge regarding the effects of exosomal miRNAs in THCA is still limited. This report intended to probe the regulatory effects of exosomal miR-152 on THCA and the underlying mechanism.

Methods: The expression profile of miR-152 was studied in clinical samples as well as B-CPAP and TPC-1 cells. Transwell, CCK-8, and flow cytometric assays were performed to investigate the roles of miR-152 on invasion, migration, proliferation, and apoptosis in B-CPAP and TPC-1 cells. The putative target of miR-152 was predicted using the bioinformatic analysis, and the targeting relationship was confirmed verified subsequently. Afterward, exosomes were isolated from bone marrow mesenchymal stem cells (BM-MSCs) and co-cultured with B-CPAP and TPC-1 cells to explore the function of exosomal miR-152 on THCA cells.

Results: miR-152 was reduced in THCA tissues and cells. Restoration of miR-152 inhibited proliferation, invasion and migration of B-CPAP and TPC-1 cells, but promoted cell apoptosis. Dipeptidyl dipeptidase 4 (DPP4), a target of miR-152, was found to promote THCA cell invasion and migration. miR-152 ferried by BM-MSCs-derived exosomes repressed THCA cell invasion and migration, and pcDNA-DPP4 weakened the repression effect.

Conclusion: Exosomal miR-152 inhibited proliferation, migration and invasion of THCA cells by binding with DPP4, which may represent a novel target for the treatment of THCA.

Keywords: Bone marrow mesenchymal stem cells; DPP4; Exosome; Thyroid carcinoma; microRNA-152.

MeSH terms

  • Adult
  • Binding Sites / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Dipeptidyl Peptidase 4 / genetics*
  • Dipeptidyl Peptidase 4 / metabolism
  • Exosomes / metabolism
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Mesenchymal Stem Cells / metabolism
  • MicroRNAs / metabolism
  • MicroRNAs / physiology*
  • Middle Aged
  • Neoplasm Invasiveness
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology*

Substances

  • MIRN152 microRNA, human
  • MicroRNAs
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4