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RNA-dependent protein kinase is required for interferon-γ-induced autophagy in MG63 osteosarcoma cells

Jie Xu1, Yuqing Ji2, Kristen L Shogren3

  • 1Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA; Musculoskeletal Center, Peking University People's Hospital, Beijing, China.

Gene
|August 5, 2021
PubMed

Insights

Interferon-gamma (IFN-γ) triggers autophagy, a cellular recycling process, in osteosarcoma cells. This IFN-γ-induced autophagy requires RNA-dependent protein kinase (PKR) but is separate from its cell death effects.

Area of Science:

  • Oncology
  • Cell Biology
  • Immunology

Background:

  • Osteosarcoma is a prevalent bone cancer in children and adolescents.
  • Interferons (IFNs) show potential antitumor activity against osteosarcoma.
  • The precise molecular pathways of IFN action in osteosarcoma remain unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms of Interferon-gamma (IFN-γ) in osteosarcoma cells.
  • To investigate the role of IFN-γ in inducing autophagy and cell death.
  • To determine the involvement of RNA-dependent protein kinase (PKR) in IFN-γ's effects.

Main Methods:

  • Treatment of osteosarcoma cells with IFN-γ.
  • Analysis of autophagosome accumulation and autophagy marker conversion (LC3-I to LC3-II).
  • Assessment of RNA-dependent protein kinase (PKR) activity and its role in IFN-γ-mediated effects.

Main Results:

  • IFN-γ induces autophagosome accumulation in osteosarcoma cells.
  • IFN-γ treatment promotes the conversion of LC3-I to LC3-II, indicating autophagy activation.
  • PKR activity is essential for IFN-γ-induced autophagy but not for IFN-γ-mediated cell death.

Conclusions:

  • IFN-γ exerts dual effects on osteosarcoma cells, inducing both autophagy and cell death.
  • PKR is a key mediator of IFN-γ-induced autophagy.
  • Understanding these differential mechanisms may inform novel therapeutic strategies for osteosarcoma.
Keywords:
AutophagyInterferon-γOsteosarcomaPKR

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