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Updated: Oct 15, 2025

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
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.
Abstract:
Tumor-associated macrophages (TAMs) are known to participate in osteosarcoma (OS) progression. As demonstrated in our previous research, miR-363 played a tumor inhibitory effect in OS cells via lowering the PDZ domain containing 2 (PDZD2) expression. The regulatory roles of TAMs on miR-363/PDZD2 and the internal mechanism relating to long noncoding RNA p53 upregulated regulator of P53 levels (lncRNA PURPL) are examined in this study. TAM-like macrophages were formed by inducing CD14+ peripheral blood mononuclear cells (PBMCs). The TAMs migration was detected after MG-63 cells transfected with miR-363 mimics or inhibitors. We then analyzed the regulatory activity of PURPL on miR-363 expression. We also tested the influences of PURPL overexpression/knockdown on MG-63 cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), as well as TAMs migration. Silence in PDZD2 expression was used to confirm the effects of PURPL on MG-63 cells. We successfully induced TAM-like macrophages. MG-63 cells transfecting miR-363 mimics suppressed TAMs migration while transfecting a converse effect was seen in miR-363 inhibitor. TAMs raised PURPL expression in MG-63 cells, which was an upstream regulator of miR-363. Along with TAMs migration, PURPL overexpression promoted MG-63 cell proliferation, migration, invasion, and EMT. An opposite influence was seen due to the PURPL knockdown. The silence of PDZD2 weakened the influences of PURPL overexpression on MG-63 cells and TAMs migration. On modulating the PURPL/miR-363/PDZD2 axis, TAMs-promoted OS development might be achieved.
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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