miR-92a-1-5p enriched prostate cancer extracellular vesicles regulate osteoclast function via MAPK1 and FoxO1

Quick Facts

  • Publication title: miR-92a-1-5p enriched prostate cancer extracellular vesicles regulate osteoclast function via MAPK1 and FoxO1
  • Journal: J EXP CLIN CANC RES
  • Year: 2023
  • DOI: 10.1186/s13046-023-02685-2
  • PMID/PMCID: 37131239; PMC10152631

Research overview

In the present study, we focused on engineering miR-92a-1-5p into EVs and determining any therapeutic roles and mechanisms of the engineered EVs. These experiments suggest that miR-92a-1-5p enriched EVs regulate osteoclast function via reduction of MAPK1 and FoxO1.

Key findings

Stable overexpression cells of miRNA-92a-5p was associated with EVs upregulating this microRNA, as confirmed by qPCR.

Further, miR-92a-1-5p enriched EVs promote osteoclast differentiation in vitro by reducing MAPK1 and FoxO1 expression, associated with increased osteoclast function as shown by TRAP staining and mRNA expression of osteoclast functional genes.

siRNA targeting MAPK1 or FoxO1 resulted in similar increase in osteoclast function.

injection promote osteolysis, which was associated with reduction of MAPK1 and FoxO1 expression in bone marrow.

Study design

A stable prostate cancer cell line (MDA PCa 2b) overexpressing miR-92a-1-5p was constructed by lentivirus, and EVs were isolated by ultracentrifugation.

The overexpression of miR-92a-1-5p in both cells and EVs was tested using qPCR.

Osteoclast function was evaluated by Trap staining, mRNA expression of osteoclastic markers ctsk and trap, immunolabeling of CTSK and TRAP and microCT using either in vitro and in vivo assays.

Echo Biotech Role

Echo Biotech contributed EV characterization.

Related platforms: Exoomics®

Related services and capabilities: EV Basic Characterization (TEM/NTA/WB)

References

Original publication: miR-92a-1-5p enriched prostate cancer extracellular vesicles regulate osteoclast function via MAPK1 and FoxO1 Journal of experimental & clinical cancer research. 2023. DOI: 10.1186/s13046-023-02685-2. PMID/PMCID: 37131239; PMC10152631.