Effect of tumor-associated macrophages on lncRNA PURPL/miR-363/PDZD2 axis in osteosarcoma cells

Fan He1, Guoming Ding2, Wu Jiang2

  • 1Department of Orthopedics, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, 261 HuanSha Road, ShangCheng, HangZhou, ZheJiang, 310006, China. FHe_Doc_29@yeah.net.

Cell Death Discovery
|October 23, 2021
PubMed

Insights

Tumor-associated macrophages promote osteosarcoma by upregulating lncRNA PURPL, which inhibits miR-363 and increases PDZD2 expression. This pathway drives tumor progression and migration.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Tumor-associated macrophages (TAMs) are key players in osteosarcoma (OS) progression.
  • Previous studies indicated miR-363 inhibits OS cell growth by reducing PDZ domain containing 2 (PDZD2) expression.

Purpose of the Study:

  • To investigate the regulatory roles of TAMs on the miR-363/PDZD2 axis in osteosarcoma.
  • To elucidate the mechanism involving the long noncoding RNA p53 upregulated regulator of P53 levels (lncRNA PURPL) in TAM-mediated OS progression.

Main Methods:

  • TAM-like macrophages were generated from CD14+ peripheral blood mononuclear cells (PBMCs).
  • MG-63 cells were transfected with miR-363 mimics or inhibitors to assess TAM migration.
  • The regulatory effect of PURPL on miR-363 expression and its influence on MG-63 cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and TAM migration were analyzed.
  • PDZD2 knockdown was used to confirm PURPL's effects.

Main Results:

  • TAM-like macrophages were successfully induced.
  • miR-363 mimics suppressed TAM migration, while inhibitors promoted it.
  • TAMs increased PURPL expression in MG-63 cells, identifying PURPL as an upstream regulator of miR-363.
  • PURPL overexpression enhanced MG-63 cell proliferation, migration, invasion, EMT, and TAM migration, while knockdown had opposite effects.
  • PDZD2 silencing attenuated the effects of PURPL overexpression on MG-63 cells and TAM migration.

Conclusions:

  • TAMs promote osteosarcoma development by modulating the PURPL/miR-363/PDZD2 axis.
  • The lncRNA PURPL acts as a crucial mediator in TAM-driven osteosarcoma progression.
  • Targeting the PURPL/miR-363/PDZD2 pathway could offer therapeutic strategies for osteosarcoma.

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